Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Scand J Immunol ; 73(5): 465-77, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21272050

RESUMEN

Prior studies of classical 24 h responses in TNP-Cl (picryl chloride) allergic contact sensitivity (CS), showed mediation by Th1 cells in CBA mice, and established that 24 h elicitation of responses requires an early 2 h CS-initiating component dependent on iNKT cells, IL-4 and B-1 B cells. Here, we studied the other form of cytotoxic T cell (Tc1) CS in DNFB sensitized BALB/c mice and determined that similar CS-initiation also is required. We systematically tested each step of the initiation pathway in this model. Thus, DNFB Tc1 CS was significantly impaired in iNKT cell deficient CD1d(-/-) and Jα18(-/-) mice, IL4Rα(-/-) and STAT-6(-/-) mice, and also in pan B-cell deficient JH(-/-) mice. Further, the Tc1 DNFB CS-initiating component, like Th1 response to TNP-Cl, was elicited by only 1-day after immunization, due to B-1 cells. In summary, we show that CS-Initiation also is required in Tc1 CS. Further, we have newly determined regulatory support of both the early and late components of DNFB induced Tc1 CS by iNKT cells and γδ-T cells. In summary, both iNKT cells and assisting γδ-T cells are involved in initiating and effector phases of DNFB induced CS.


Asunto(s)
Dermatitis por Contacto/inmunología , Células T Asesinas Naturales/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Linfocitos T Citotóxicos/inmunología , Traslado Adoptivo/métodos , Animales , Dinitrofluorobenceno , Femenino , Citometría de Flujo , Inmunización/métodos , Inmunofenotipificación , Interferón gamma/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Organismos Libres de Patógenos Específicos
2.
Scand J Immunol ; 74(1): 52-61, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21352253

RESUMEN

Natural killer T cells with invariant αß-T cell receptors (TCRs) (iNKT cells) constitute a lipid-responsive arm of the innate immune system that has been implicated in the regulation or promotion of various immune, infectious and neoplastic processes. Contact sensitivity (CS), also known as contact hypersensitivity or allergic contact dermatitis, is one such immune process that begins with topical sensitization to an allergen and culminates in a localized cutaneous inflammatory response after challenge with the same allergen. CS depends on events initiated early in sensitization by hepatic iNKT cells. We have shown previously that these iNKT cells release IL-4 early after skin sensitization to activate B-1 B cells to produce IgM antibodies that aid in local recruitment of the effector T cells. Here, we utilize adoptive transfer techniques in several strains of knockout mice to demonstrate that hepatic lipids isolated 30 min after sensitization are significantly more stimulatory to naïve hepatic iNKT cells than hepatic lipids isolated after sham sensitization. These stimulatory hepatic lipids specifically affect iNKT cells and not B-1 B cells. The downstream CS response is abrogated with anti-CD1d-blocking antibodies, suggesting a critical role of CD1d in the activation of hepatic iNKT cells with these lipids. Hepatocytes may not be essential, as donor hepatic iNKT cells can reconstitute CS without migrating to the recipient mouse liver. Rather, CD1d-expressing liver mononuclear cells are sufficient for activation of iNKT cells. In conclusion, stimulatory lipids accumulate in the liver soon after sensitization and facilitate iNKT cell activation in a CD1d-dependent yet potentially hepatocyte-independent manner.


Asunto(s)
Antígenos CD1d/inmunología , Dermatitis por Contacto/inmunología , Lípidos/inmunología , Hígado/inmunología , Activación de Linfocitos , Células T Asesinas Naturales/inmunología , Traslado Adoptivo , Animales , Antígenos CD1d/genética , Hepatocitos/inmunología , Ratones , Ratones Noqueados
3.
J Exp Med ; 138(5): 1144-55, 1973 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-4744921

RESUMEN

Cutaneous basophil hypersensitivity, an immune inflammatory reaction characterized by infiltrates of basophils and a delayed time-course, was studied in guinea pigs contact sensitized with oxazolone. Routine histological techniques, employing ordinary paraffin sections, were modified to study this reaction. When biopsies of contact lesions were processed by these methods dense infiltrates of basophils could be demonstrated. Animals sensitized with complete Freund's adjuvant emulsified with oxazolone-keyhole limpet hemocyanin conjugates also developed delayed-in-time responses to contact challenge with oxazolone but not to picryl chloride. These hapten-specific delayed-in-time reactions also contained substantial numbers of basophils. Transfer of serum from actively sensitized guinea pigs resulted in specific accumulation of basophils at challenge sites of recipients. Thus, in this experimental system, cutaneous basophil hypersensitivity was found to be a hapten-specific delayed-in-time reaction that could be transferred with immune serum.


Asunto(s)
Basófilos/inmunología , Dermatitis por Contacto/inmunología , Hipersensibilidad Tardía/inmunología , Sueros Inmunes , Inmunidad Materno-Adquirida , Piel/inmunología , Adyuvantes Inmunológicos , Animales , Dermatitis por Contacto/patología , Éteres de Etila , Hipersensibilidad Tardía/inducido químicamente , Hipersensibilidad Tardía/patología , Ratones , Microscopía Electrónica , Oxazoles
4.
J Exp Med ; 157(5): 1604-17, 1983 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-6602201

RESUMEN

In four different systems it was shown that murine delayed-type hypersensitivity (DTH) responses at 18-48 h were preceded by early 2-h responses. CBA mice immunized with picryl chloride, BDF1 mice immunized with oxazolone, BALB/c mice immunized with dinitrofluorobenzene, and C57BL/6 mice immunized with L5178Y lymphoma cells, and challenged with the appropriate specific antigen, all gave rise to expected 18-48 h delayed-in-time hypersensitivity reactions, but all of these responses were preceded by early hypersensitivity reactions that peaked at 2 h. These early 2-h reactions are transferable with T cells or with a T cell-derived, antigen-binding factor and are antigen-specific. The early and late components of DTH reactions are mast cell dependent since neither are elicited in mast cell deficient W/Wv or Sl/Sld mice. The T cell activity mediating the early component of DTH is demonstrable as early as 24 h after immunization, while the classical late component of DTH is not demonstrable until days 3-4. The difference in onset after immunization of the early and late components of DTH, and the different kinetics of these components in recipients of cell transfers that were challenged immediately or 24 h after transfer, led to the hypothesis that immunization for DTH leads to rapid induction in lymphoid organs of a certain population of T cells to produce an antigen-binding factor. This factor sensitizes peripheral tissues, probably mast cells, and local challenge with appropriate antigen leads to mast cell activation and release of the vasoactive amine serotonin, resulting in increased permeability of the local vasculature. This allows other circulating antigen-specific T cells, which are induced later after immunization, to enter the tissues and interact with antigen, resulting in production of chemoattractant lymphokines that recruit accessory leukocytes such as monocytes and polymorphs to enter the tissues via gaps between endothelial cells. These inflammatory cells, that are recruited to the site via two different T cell activities, constitute the characteristic infiltrate of DTH responses. Identification of an early 2-h component of DTH that is T cell- and mast cell-dependent provides evidence that the tissue-sensitizing, antigen-binding, T cell factor probably functions in vivo in the early phases of DTH responses.


Asunto(s)
Hipersensibilidad Tardía/inmunología , Mastocitos/inmunología , Linfocitos T/inmunología , Animales , Suero Antilinfocítico/farmacología , Hipersensibilidad Tardía/diagnóstico , Inmunidad Activa , Inmunización Pasiva , Linfocinas/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Factores Supresores Inmunológicos , Factores de Tiempo
5.
J Exp Med ; 156(1): 159-72, 1982 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-6177818

RESUMEN

Guinea pigs immunized with protein antigens emulsified with complete Freund's adjuvant (CFA) and skin tested at 3-4 wk have classical tuberculin-type delayed hypersensitivity (DH) reactions with few basophils present. However, recipients of T cells from these animals have delayed responses containing large basophil infiltrates and thus resemble basophil-rich cutaneous basophil hypersensitivity (CBH) responses that are elicited in animals immunized without CFA. This suggests that animals immunized with CFA have T cells with basophil-recruiting capacity but that this activity is suppressed. Using a transfer system, we found that immune serum from donors immunized with CFA had the ability to suppress the basophil-recruiting capacity of immune T cells. When immune serum and peritoneal exudate cells from guinea pigs immunized with CFA were co-transferred intravenously to normal recipients, the cell-mediated transfer of basophil-rich responses was suppressed. The responsible serum factor was antigen nonspecific, had an approximately 70,000 mol wt, and acted preferentially on cells from donors that express basophil-poor DH responses. Thus, tuberculin-type delayed hypersensitivity and CBH might be mediated by a common T cell, but the resulting basophil component of the delayed response depends on the modulation of T cell recruitment of basophils by factors in CFA-immune serum.


Asunto(s)
Basófilos/inmunología , Hipersensibilidad Tardía/inmunología , Terapia de Inmunosupresión , Linfocitos T/inmunología , Animales , Fraccionamiento Químico , Epítopos , Femenino , Adyuvante de Freund/farmacología , Cobayas , Hemocianinas/inmunología , Sueros Inmunes/farmacología , Inmunización Pasiva , Mycobacterium tuberculosis/inmunología , Oxazolona/inmunología , Pruebas Cutáneas , Factores de Tiempo
6.
J Exp Med ; 157(3): 862-73, 1983 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-6187880

RESUMEN

T cell-dependent activation of resident tissue mast cells is required for the elicitation of delayed-type hypersensitivity skin reactions in mice. A T cell-derived antigen-binding factor that transfers the ability to elicit an immediate hypersensitivity-like skin reaction is described and compared with a hybridoma IgE antibody. Both the T cell factor and IgE mediate reactions with increased vascular permeability and both are mast cell dependent, as they are inactive in two different types of mast cell deficient mice (W/Wv and Sl/Sld). The T cell factor was distinguished from IgE by affinity chromatography using specific anti-IgE and anti-factor antibodies and by a shorter duration of passive sensitization. The T cell factor is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity.


Asunto(s)
Anticuerpos Antiidiotipos/biosíntesis , Sitios de Unión de Anticuerpos , Inmunoglobulina E/inmunología , Linfocinas/biosíntesis , Linfocitos T/inmunología , Animales , Anticuerpos Antiidiotipos/análisis , Anticuerpos Antiidiotipos/inmunología , Unión Competitiva , Cromatografía de Afinidad , Epítopos , Hipersensibilidad Tardía/etiología , Hipersensibilidad Tardía/inmunología , Inmunización Pasiva , Inmunoglobulina E/análisis , Inmunoglobulina E/biosíntesis , Linfocinas/análisis , Linfocinas/inmunología , Masculino , Mastocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Mutantes , Oxazolona/inmunología , Cloruro de Picrilo/inmunología , Factores Supresores Inmunológicos
7.
J Exp Med ; 142(3): 732-47, 1975 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-1165473

RESUMEN

The skin sites of the mouse where delayed-type hypersensitivity (DTH) reactions are most easily elicited (foot pads and ears) are particularly rich in 5-hydroxytryptamine (5-HT)-containing mast cells. Since mice are deficient in circulating basophils, which play a role in at least some DTH reactions, we investigated the possibility that the mast cells were playing an important role in the evolution of the skin reactions of DTH in mice. We found that reserpine, a drug which depletes mast cells of 5-HT, abolished the ability of the mouse to make DTH reactions in the skin. The suppressive effect of reserpine could be partially blocked by monoamine oxidase inhibitors which prevent the degradation of 5-HT in the cytosol of the mast cell. Spleen cells of immune, reserpine-treated mice transferred DTH reactions to nonimmune mice normally, indicating that the reserpine treatment did not affect immune T cells. DTH reactions could not be transferred into reserpine-treated mice. We suggest that T cells are continually emigrating from the blood, through postcapillary venule endothelium, by a mechanism which does not depend on vasoactive amines. If they are appropriately immune and meet the homologous antigen in the tissue, they induce mast cells to release vasoactive amines which cause postcapillary venule endothelial cells to separate, allowing the egress from the blood of cells which ordinarily do not recirculate. The secondarily arriving vasoactive amine-dependent cells are responsible for the micro- and macroscopic lesions of DTH reactions. Chemotactic factors may also be involved in bringing cells to the DTH reaction sites but we propose that T-cell regulation of vasoactive amine-containing cells allows the effector cells to pass through the endothelial gates after they are called.


Asunto(s)
Hipersensibilidad Tardía , Mastocitos/análisis , Serotonina/análisis , Animales , Antígenos/administración & dosificación , Oído/análisis , Eritrocitos/inmunología , Miembro Posterior/análisis , Inyecciones Intravenosas , Masculino , Mastocitos/citología , Ratones , Inhibidores de la Monoaminooxidasa/farmacología , Oxazolona/inmunología , Reserpina/farmacología , Serotonina/metabolismo , Ovinos/inmunología , Pruebas Cutáneas , Factores de Tiempo
8.
J Exp Med ; 141(3): 697-702, 1975 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-1117258

RESUMEN

Mice immunized with more SRBC than are required to produce optimal delayed-type hypersensitivity reactions, developed good antibody responses and poor delayed foot pad reactions. Cyclophosphamide treatment in low doses (20 mg/kg) before immunization, augmented the delayed-type hypersensitivity without affecting antibody responses. Cyclophosphamide did not augment delayed responses to optimal doses of SRBC (0.01%), but did augment the delayed hypersensitivity response of mice immunized with a suboptimal antigen dose (0.001%); which produced no detectable antibody response with or without cyclophosphamide pretreatment. These results suggest that antibody feedback is not the sole regulator of delayed reactions; the possibility that suppressor T cells may also be involved is discussed.


Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Ciclofosfamida/administración & dosificación , Hipersensibilidad Tardía/inmunología , Animales , Ciclofosfamida/inmunología , Ciclofosfamida/farmacología , Eritrocitos/inmunología , Retroalimentación , Gansos/inmunología , Miembro Posterior , Caballos/inmunología , Humanos , Masculino , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos NZB , Ovinos/inmunología
9.
J Exp Med ; 146(5): 1390-404, 1977 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-72778

RESUMEN

Shortly after intravenous immunization of mice with heterologous erythrocytes (RBC) antigen-specific Thy 1+ cells which form rosettes with the immunizing RBC (thymic-derived lymphocytes-forming rosettes [T-RFC]) appear in the spleen. These T-RFC are much less stable than Thy 1- RFC (non-thymic-derived [B-RFC]) although most if not all of both classes of RFC adhere to nylon. T-RFC are induced with low doses of antigen (which fail to induce B-RFC) and are inhibited by higher antigen doses which are optimal for induction of B-RFC. Pretreatment of mice with cyclophosphamide prevents the high dose inhibition of T-RFC. Although there are many parallels between the production of T-RFC and delayed-type hypersensitivity (DTH) it is unlikely that the T-RFC are essential for DTH reactions since DTH can be transferred with cells which pass through nylon, and such cells are almost totally depleted of T-RFC. Thus immunization can lead to the production of large numbers of antigen-specific T-RFC whose functional role in the immune response is unknown. However, the characteristics of the T-RFC suggest that they may play an important role in amplification of suppressor cell activity.


Asunto(s)
Antígenos , Formación de Roseta , Linfocitos T/inmunología , Animales , Antígenos/administración & dosificación , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Adhesión Celular , Separación Celular , Ciclofosfamida/farmacología , Relación Dosis-Respuesta Inmunológica , Epítopos , Glutaral/farmacología , Hipersensibilidad Tardía/inmunología , Masculino , Ratones , Bazo/inmunología , Linfocitos T/efectos de los fármacos
10.
J Exp Med ; 152(5): 1358-74, 1980 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-6968811

RESUMEN

We have previously suggested that the release of serotonin (5-hydroxytryptamine) (5-HT) by local tissue mast cells is required for the elicitation of delayed-type hypersensitivity (DTH) in mice. In the current study, light microscopic radioautographs from animals treated with [3H]5-HT indicated that local mast cells released 5-HT between 6 and 18 h during the evolution of DTH. Ultrastructural examination of mast cells revealed surface activation, indicated by extension of surface filopodia, and degranulation by fusion and exocytosis. Light and electron microscopic studies of the endothelium of postcapillary venules at sites of DTH revealed the development of gaps between adjacent cells. The development of gaps permitted extravasation of tracers that was abolished by depletion or antagonism of 5-HT. Thus mast cells degranulated and released 5-HT in DTH, and this 5-HT acted on local vessels. Recipients of nonadherent, non-immunoglobulin-bearing sensitized lymphocytes also demonstrated similar mast cell degranulation and the formation of endothelial gaps. This indicated that mast cell degranulation and 5-HT release in murine DTH were probably T cell dependent.


Asunto(s)
Hipersensibilidad Tardía/inmunología , Mastocitos/inmunología , Serotonina/metabolismo , Linfocitos T/inmunología , Animales , Gránulos Citoplasmáticos/ultraestructura , Endotelio/ultraestructura , Mastocitos/ultraestructura , Ratones , Microscopía Electrónica , Piel/citología , Vénulas/ultraestructura
11.
J Exp Med ; 151(2): 362-75, 1980 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-7356727

RESUMEN

Three outcomes pertinent to contact sensitivity (CS) follow immunization with various forms of trinitrophenylated (TNP) substrates: (a) specific immunological unresponsiveness for CS is induced when immunization favors activation of splenic suppressor cells. This state is achieved by intravenous injection of trinitrophenyl-conjugated to various types of cells, such as peritoneal exudate cells (PEC). (b) A short-lived or evanescent form of CS is induced when immunization reduces activation of the suppressor circuit. This can be achieved by subcutaneous immunization with trinitrophenyl conjugated to syngeneic PEC, by pretreatment with cyclophosphamide to diminish suppression before intravenous immunization, or by altering the mode of antigen presentation by using TNP-substrate that has undergone phagocytosis. (c) A long-lived form of CS is induced when trinitrophenyl is presented to the immune system on skin cells either by contact skin painting with reactive trinitrophenyl, or by subcutaneous, or even intravenous injection of trinitrophenyl-conjugated epidermal cells. In fact, trinitrophenyl-conjugated epidermal cells induced CS even when the suppressor circuit was activated by intravenous coadministration of TNP-PEC. This implies that antigen presentation on epidermal cells induces sensitized cells that are relatively resistant to suppression. The cell type(s) in the skin that are primarily responsible for this potent form of antigen presentation are most likely Langerhans cells, because they can be concentrated by virtue of their Fc receptors and they are Ia positive. Thus, both the anatomical site where antigen is first encountered by the immune apparatus, as well as the nature of the cells which present the antigen, determine whether a CS response will ensue, as well as whether it will be evanescent or long-lasting.


Asunto(s)
Antígenos/administración & dosificación , Dermatitis por Contacto/etiología , Hipersensibilidad Tardía , Animales , Anticuerpos/administración & dosificación , Líquido Ascítico/citología , Ciclofosfamida/farmacología , Femenino , Tolerancia Inmunológica , Inmunización Pasiva , Masculino , Ratones , Ratones Endogámicos CBA , Fagocitosis , Piel/inmunología , Factores de Tiempo
12.
J Exp Med ; 155(5): 1344-56, 1982 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-6461712

RESUMEN

We have tested the ability of several types of trinitrophenyl (TNP)-labeled Ia+ cells to induce contact hypersensitivity (CS) after intravenous injection. Most labeled cell types (spleen cells, splenic macrophages, various types of peritoneal-exudate cells) not only fail to induce CS after this type of inoculation but, rather, activate T suppressor cells leading to specific immunological tolerance. Occasionally, some of these immunizing cells managed to bypass the T suppressor system and induced CS. In those cases the response was short-lived and could be blocked by concomitant injection of trinitrobenzelsulphonic acid (TNBS), a potent inducer of T suppressor cells. In sharp contrast to these results, TNP-labeled splenic dendritic cells and TNP-labeled peritoneal-exudate cells induced by complete Freund's adjuvant had the following distinctive features: (a) They were always able to sensitize when injected intravenously, and the degree of sensitization they produced was roughly equivalent to that achieved by cutaneous application of picryl chloride, the chemically reactive form of TNP. (b) The response they elicited was long lived (i.e., lasted for greater than 3 wk). (c) Their sensitizing capacity could not be blocked by the concomitant injection of TNBS. (d) They elicited a response that could be adoptively transferred to untreated, normal recipients. These results indicate that the type of cell that first presents antigen to the immune system plays an important, even essential, role in determining the strength and duration of the subsequent immune response. In particular, the results suggest that some special antigen-presenting cells can induce a response that is relatively resistant to host suppressor mechanisms. Evidence that they do so by activating contrasuppressor cells is discussed.


Asunto(s)
Antígenos/inmunología , Líquido Ascítico/citología , Bazo/citología , Linfocitos T/inmunología , Animales , Líquido Ascítico/inmunología , Dermatitis por Contacto/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Adyuvante de Freund/farmacología , Tolerancia Inmunológica , Inmunidad Celular , Inmunización Pasiva , Activación de Linfocitos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos CBA , Mycobacterium/inmunología , Bazo/inmunología , Linfocitos T Reguladores/inmunología , Trinitrobencenos/inmunología , Ácido Trinitrobencenosulfónico/inmunología
13.
J Exp Med ; 184(6): 2129-39, 1996 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-8976169

RESUMEN

Contact sensitivity (CS) responses to reactive hapten Ag, such as picryl chloride (PCl) or oxazolone (OX), are classical examples of T cell-mediated immune responses in vivo that are clearly subject to multifaceted regulation. There is abundant evidence that downregulation of CS may be mediated by T cells exposed to high doses of Ag. This is termed high dose Ag tolerance. To clarify the T cell types that effect CS responses and mediate their downregulation, we have undertaken studies of CS in mice congenitally deficient in specific subsets of lymphocytes. The first such studies, using alpha beta T cell-deficient (TCR alpha -/-) mice, are presented here. The results clearly show that TCR alpha -/- mice cannot mount CS, implicating alpha beta T cells as the critical CS-effector cells. However, TCR alpha -/- mice can, after high dose tolerance, downregulate alpha +/+ CS-effector T cells adoptively transferred into them. By mixing ex vivo and then adoptive cell transfers in vivo, the active downregulatory cells in tolerized alpha -/- mice are shown to include gamma delta TCR+ cells that also can downregulate interferon-gamma production by the targeted CS-effector cells in vitro. Downregulation by gamma delta cells showed specificity for hapten, but was not restricted by the MHC. Together, these findings establish that gamma delta T cells cannot fulfill CS-effector functions performed by alpha beta T cells, but may fulfill an Ag-specific downregulatory role that may be directly comparable to reports of Ag-specific downregulation of IgE antibody responses by gamma delta T cells. Comparisons are likewise considered with downregulation by gamma delta T cells occurring in immune responses to pathogens, tumors, and allografts, and in systemic autoimmunity.


Asunto(s)
Dermatitis por Contacto , Interferón gamma/biosíntesis , Receptores de Antígenos de Linfocitos T alfa-beta/deficiencia , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T/inmunología , Traslado Adoptivo , Animales , Células Presentadoras de Antígenos/inmunología , Células Cultivadas , Regulación hacia Abajo , Tolerancia Inmunológica , Inmunización , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Endogámicos , Ratones Noqueados , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/biosíntesis , Bazo/inmunología
14.
J Exp Med ; 186(7): 1015-26, 1997 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-9314551

RESUMEN

Complement (C) is an important component of innate immunity, and was also shown recently to participate in induction of acquired B cell humoral immunity. In this study, we present evidence that C also participates in acquired T cell immunity. We found that C was involved in early events of the efferent elicitation phase of contact sensitivity (CS), and delayed-type hypersensitivity (DTH). Thus, CS and DTH were inhibited by administration of a C-blocker, soluble recombinant C receptor-1 (sCR1), when given 30 min before, but not 3 h after local antigen challenge. Among C components, local C5 were thought crucial to elicitation of CS, since local administration of anti-C5 monoclonal antibodies or locally injected C-depleting cobra venom factor also inhibited CS and DTH. These findings were consistent with our previous finding of the importance of C5 for CS elicitation, using congenitally C5-deficient mice. To dissect the mechanism of C dependence in CS, we demonstrated that locally increased early macrophage chemotactic activity (probably C5a) in evolving CS skin extracts, as well as late elaboration of IFN-gamma, were both inhibited by anti-C treatment. In addition, histological analysis showed that leukocyte recruitment into CS ear sites was similarly C-dependent. Furthermore, an initiating role of B cell-derived C-fixing immunoglobulin was suggested by demonstration of impaired CS responses in B cell-deficient mice. In summary, these results suggest that C was activated locally, perhaps via a B cell product, in an important early component of the stepwise events necessary to elicit CS, leading to local production of C5-dependent macrophage chemotactic activity and later IFN-gamma, and subsequently leading to cell infiltration, for development of T cell-dependent CS.


Asunto(s)
Linfocitos B/inmunología , Activación de Complemento/inmunología , Complemento C5/inmunología , Dermatitis por Contacto/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Factores Quimiotácticos/biosíntesis , Quimiotaxis , Complemento C5/metabolismo , Proteínas Inactivadoras de Complemento/inmunología , Proteínas Inactivadoras de Complemento/farmacología , Venenos Elapídicos/farmacología , Femenino , Hipersensibilidad Tardía/inmunología , Interferón gamma/biosíntesis , Macrófagos/fisiología , Ratones , Ratones Endogámicos , Receptores de Complemento/inmunología , Proteínas Recombinantes/farmacología , Piel/inmunología , Linfocitos T/metabolismo
15.
J Cell Biol ; 93(3): 638-47, 1982 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7118996

RESUMEN

We studied binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells. We found two types of serotonin binding protein in RBL cells. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 X 10(-6) M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD1 = 4.5 X 10(-8) M; KD2 = 3.9 X 10(-6) M) did not bind to Con A. Moreover, binding of [3H]serotonin to protein of peak I was sensitive to inhibition by reserpine, while binding of [3H]serotonin to protein of peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract peak I than peak II protein. Neither peak I nor peak II protein resembled the serotonin binding protein (SBP) that is found in serotonergic neurons of the brain and gut. Electron microscope radioautographic analysis of the intracellular distribution of [3H]serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules. No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but peak I protein may be associated with the granular membrane while peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.


Asunto(s)
Basófilos/metabolismo , Proteínas Portadoras/metabolismo , Leucemia Experimental/metabolismo , Mastocitos/metabolismo , Serotonina/metabolismo , Animales , Células Cultivadas , Concanavalina A/metabolismo , Gránulos Citoplasmáticos/metabolismo , Gangliósidos/farmacología , Membranas Intracelulares/metabolismo , Masculino , Ratones , Ratas , Reserpina/metabolismo
16.
J Clin Invest ; 58(5): 1145-54, 1976 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-791969

RESUMEN

Jones-Mote reactions are delayed, erythematous, and mildly indurated cutaneous reactions originally described in humans sensitized by skin injection of heterologous proteins. Similar reactions in guinea pigs contain many basophils and are called cutaneous basophil hypersensitivity. In contrast, guinea pigs immunized with mycobacterial adjuvants have classical tuberculin-type delayed hypersensitivity reactions, which contain few basophils. This has led to a new classification of delayed responses, based largely on the presence or absence of basophils. We induced sensitization for Jones-Mote reactions in 20 normal humans by intradermal injections of keyhole limpet hemocyanin. Skin tests with KLH 1 wk later showed erythematous and indurated delyaed reactions in all subjects. Rebuck skin windows showed specific accumulations of basophils with a delayed time-course in 18 of 20 subjects. In 12 normals sensitized with oxazolone-keyhole limpet hemocyanin conjugates, skin reactions and in vitro lymphocyte stimulation showed carrier and not hapten specificity, suggesting that cutaneous responses were probably mediated by T cells. A comparative study of strongly positive PPD skin tests in patients with tuberculosis showed significant basophil accumulations in five of nine subjects. Thus, basophils occurred in human tuberculin and Jones-Mote reactions and were not a distinguishing feature of Jones-Mote reactions. We suggest that the occurrence of basophils at delayed reactions is under complex regulation and that basophil accumulations are an aspect of delayed hypersensitivity, rather than an indication of a distinctive and separate response.


Asunto(s)
Basófilos/inmunología , Hipersensibilidad Tardía/inmunología , Adulto , Antígenos , Femenino , Hemocianinas/inmunología , Humanos , Linfocitos/inmunología , Masculino , Pruebas Cutáneas , Técnica de Ventana Cutánea , Prueba de Tuberculina
17.
J Clin Invest ; 100(3): 629-38, 1997 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-9241124

RESUMEN

To investigate the cellular immune events contributing to airway hyperreactivity (AHR), we studied an in vivo mouse model induced by the hapten picryl (trinitrophenyl) chloride (PCl). Mice were immunized by cutaneous contact sensitization with PCl and airway challenged subsequently with picryl sulfonic acid (PSA) antigen (Ag). Increased airway resistance was produced late (24 h) after Ag challenge, disappeared by 48 h, and was associated with no decrease in diffusion capacity. AHR could be produced in PCl immune/ PSA challenged mice on day 7 or even, with challenge, as early as 1 d after contact sensitization, after adoptive transfer of immune cells lacking CD3(+) contact sensitivity effector T cells, or after transfer of Ag-specific lymphoid cells depleted of conventional T lymphocytes with surface determinants for CD3, CD4, CD8, TCR-beta, or TCR-delta molecules. Further experiments showed that development of AHR depended upon transfer of immune cells expressing surface membrane Thy-1 and B220 (CD45RA) determinants. We concluded that a novel population of Ag-specific lymphoid cells with a defined surface phenotype (Thy-1(+), CD3(-), CD4(-), CD8(-), TCR-alphabeta-, TCR-gammadelta-, and CD45RA+) is required in a mouse model for the development of AHR.


Asunto(s)
Traslado Adoptivo , Asma/inmunología , Complejo CD3/inmunología , Inmunidad Celular , Antígenos Comunes de Leucocito/inmunología , Linfocitos T/inmunología , Antígenos Thy-1/inmunología , Animales , Asma/fisiopatología , Femenino , Haptenos/administración & dosificación , Haptenos/inmunología , Ratones , Ratones Endogámicos BALB C , Cloruro de Picrilo/administración & dosificación , Cloruro de Picrilo/inmunología
18.
Nat Biotechnol ; 15(8): 759-62, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9255790

RESUMEN

A human skin allograft injury model in immunodeficient mice, engrafted with human peripheral blood mononuclear cells from a different donor, has been used to test whether reagents that block human T cell CD2 interactions with its principal ligand, LFA-3 (CD58), can inhibit immune reactions in vivo. In this model, human skin grafts show a reproducible pattern of progressive human T-cell infiltration and human graft microvascular injury that resembles human first-set skin graft rejection. Murine Mab to human LFA-3 or human LFA-3-IgG1 fusion protein, but not isotype-matched control antibodies, each markedly protected skin grafts from leukocyte infiltration and injury. These data provide the first evidence that LFA-3 functions in vivo and establish the ability of this new model to test human-specific immune modulators.


Asunto(s)
Antígenos CD2/metabolismo , Antígenos CD58/metabolismo , Trasplante de Piel/inmunología , Quimera por Trasplante/inmunología , Animales , Anticuerpos Monoclonales/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Activación de Linfocitos , Ratones , Ratones SCID , Linfocitos T/inmunología , Trasplante Homólogo
19.
Curr Top Microbiol Immunol ; 252: 171-7, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11125474

RESUMEN

Although B-1 B cells have received considerable attention, their actual role in the normal functioning of the immune system is unclear. The hypothesized role of B-1 cell IgM in natural protective immunity is just being established. We have uncovered a separate and novel role for B-1 cell IgM in initiating the elicitation of acquired T cell-dependent contact sensitivity (CS), the prototype of in vivo T cell immunity, early after immunization (within 4 days). The recent recognition of a similarly unanticipated role of B cells in a variety of T cell responses, may indicate that B-1 cell IgM has a broader role in immunity than thought previously. We showed that 24 hr CS responses, and rises in local IFN-gamma levels at 24 hrs later after antigen (Ag) challenge the ears, were absent in pan B cell and antibody deficient mice. The mechanism of B cell involvement in CS-initiation is via local C5a generation early (1-2 hrs) after antigen (Ag) challenge of the ears, in 4 day contact sensitized mice. C5a activates local mast cells to release serotonin (5-HT) and TNF alpha to induce endothelial ICAM-1 and VCAM-1, leading to T cell recruitment. We hypothesized that C5a was generated via complement activation due to antibodies forming local AgAb complexes, and that B-1 cell IgM was involved because isotype switching of B-2 cells to produce C-activating IgG isotypes, could not occur as early as day 4. Indeed, B-1 cell deficient CBA/N-xid mice lacked C5a in 2 hr ear extracts, and had impaired CS ear swelling and elaboration of IFN-gamma at 24 hrs. Importantly, adoptive transfer of purified normal peritoneal B-1 cells, or just i.v. injection of Ag-specific IgM monoclonal antibodies in sensitized xid, restored deficient early C5a and late 24 hr ear swelling. These results suggest that early after Ag challenge, specific B-1 cell IgM, produced at distant sites by prior sensitization, forms AgAb complexes that trigger elaboration of C5a, to activate mast cell release of vasoactive TNF alpha and 5-HT to initiate CS, leading to T cell recruitment. We postulate that antibody of various isotypes possibly may lead to local vascular activation to aid in T cell recruitment in a variety of T cell responses, but that very early after immunization, Ag-specific IgM produced by B-1 cells, preferentially serves this important function.


Asunto(s)
Subgrupos de Linfocitos B/inmunología , Dermatitis por Contacto/inmunología , Inmunoglobulina M/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Traslado Adoptivo , Animales , Subgrupos de Linfocitos B/trasplante , Activación de Complemento , Complemento C5a/deficiencia , Complemento C5a/inmunología , Oído , Humanos , Inmunidad Innata , Inmunización , Cambio de Clase de Inmunoglobulina , Inmunoglobulina G/inmunología , Síndromes de Inmunodeficiencia/inmunología , Interferón gamma/sangre , Mastocitos/metabolismo , Ratones , Ratones Endogámicos CBA , Serotonina/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo
20.
J Invest Dermatol ; 81(1): 28-31, 1983 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6863977

RESUMEN

The growth rate of Cloudman S91 melanoma cells was compared in groups of normal and immunologically compromised DBA/2 mice that had undergone thymectomy and treatment with antilymphocyte serum. Tumor growth was markedly accelerated in the immunosuppressed animals. Other groups of normal and immunosuppressed animals were treated with daily injections of either histamine, the H-2 antihistamine cimetidine, the H-1 antihistamine pyrilamine; or the mast cell stabilizer proxicromil. Histamine treatment accelerated tumor growth, but only in normal animals and had little effect on tumor growth in immunocompromised hosts. Cimetidine treatment tended to increase tumor growth in normal hosts but this was statistically significant in only 1 of 3 experiments. In contrast, treatment with cimetidine, pyrilamine, or proxicromil always resulted in significant retardation of tumor growth in immunosuppressed animals. These data are consistent with the notion that thymectomy and treatment with antilymphocyte serum results in enhanced tumor growth that is in part due to activation of histamine-dependent suppressor cells. In this system, histamine activation of suppressor cells may be reversed by treatment with either antihistamines or proxicromil, a drug that prevents mast cell release of histamine. However, since the effects of these drugs seem to depend on the immune status of the host, thorough evaluation of immunoregulatory function and careful testing to determine whether histamine blockers reduce or promote tumor growth would seem indicated when immunomodulatory treatment with these drugs is contemplated.


Asunto(s)
Antagonistas de los Receptores Histamínicos/farmacología , Histamina/farmacología , Mastocitos/efectos de los fármacos , Melanoma/inmunología , Animales , Cromonas/farmacología , Cimetidina/farmacología , Terapia de Inmunosupresión , Masculino , Melanoma/patología , Metisergida/farmacología , Ratones , Ratones Endogámicos DBA , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , Pirilamina/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA