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1.
Nat Immunol ; 25(3): 496-511, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38356058

RESUMEN

Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (Treg) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct Treg cell populations: prototypical serum stimulation 2-positive (ST2+) Treg cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3+) Treg cells that are enriched in females. We show that the transcription factors GATA-binding protein 3 and peroxisome proliferator-activated receptor-γ, together with the cytokine interleukin-33, promote the differentiation of ST2+ VAT Treg cells but repress CXCR3+ Treg cells. Conversely, the differentiation of CXCR3+ Treg cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2+ Treg cells. Finally, we demonstrate that ST2+ Treg cells preserve glucose homeostasis, whereas CXCR3+ Treg cells restrain inflammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defines two molecularly and developmentally distinct VAT Treg cell types with unique context- and sex-specific functions.


Asunto(s)
Proteína 1 Similar al Receptor de Interleucina-1 , Linfocitos T Reguladores , Femenino , Masculino , Humanos , Grasa Intraabdominal , Citocinas , Inflamación , Glucosa
2.
Immunol Cell Biol ; 102(3): 194-211, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286436

RESUMEN

T helper 2 (Th2) cells stochastically express from the Il4 locus but it has not been determined whether allelic expression is linked or independent. Here, we provide evidence that alleles are independently activated and inactivated. We compared Il4 locus expression in T cells from hemizygous IL-4 reporter mice in culture and in vivo following exposure to type 2 immunogens. In culture, Il4 alleles had independent, heritable expression probabilities. Modeling showed that in co-expressors, dual allele transcription occurs for only short periods, limiting per-cell mRNA variation in individual cells within a population of Th2 cells. In vivo profiles suggested that early in the immune response, IL-4 output was derived predominantly from single alleles, but co-expression became more frequent over time and were tuned by STAT6, supporting the probabilistic regulation of Il4 alleles in vivo among committed IL-4 producers. We suggest an imprinted probability of expression from individual alleles with a short transcriptional shutoff time controls the magnitude of T cell IL-4 output, but the amount produced per allele is amplified by STAT6 signaling. This form of regulation may be a relevant general mechanism governing cytokine expression.


Asunto(s)
Interleucina-4 , Células Th2 , Animales , Ratones , Alelos , Citocinas , ARN Mensajero/genética
3.
Immunol Cell Biol ; 100(10): 791-804, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36177669

RESUMEN

Recent studies propose that T follicular helper (Tfh) cells possess a high degree of functional plasticity in addition to their well-defined roles in mediating interleukin-4-dependent switching of germinal center B cells to the production of immunoglobulin (Ig)G1 and IgE antibodies. In particular Tfh cells have been proposed to be an essential stage in Th2 effector cell development that are able to contribute to innate type 2 responses. We used CD4-cre targeted deletion of BCL6 to identify the contribution Tfh cells make to tissue Th2 effector responses in models of atopic skin disease and lung immunity to parasites. Ablation of Tfh cells did not impair the development or recruitment of Th2 effector subsets to the skin and did not alter the transcriptional expression profile or functional activities of the resulting tissue resident Th2 effector cells. However, the accumulation of Th2 effector cells in lung Th2 responses was partially affected by BCL6 deficiency. These data indicate that the development of Th2 effector cells does not require a BCL6 dependent step, implying Tfh and Th2 effector populations follow separate developmental trajectories and Tfh cells do not contribute to type 2 responses in the skin.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T Colaboradores-Inductores , Diferenciación Celular , Centro Germinal , Linfocitos B , Proteínas Proto-Oncogénicas c-bcl-6/genética
4.
Proc Natl Acad Sci U S A ; 115(5): 1033-1038, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29339496

RESUMEN

T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development. Sorting experiments revealed that IL-13-SP Th2 cells originated from IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5 and IL-9. In vivo, high TSLP levels acted directly on CD4+ T cells to induce the development of IL-13-SP and IL-4+IL-13+ double-positive populations in lymph node. These cells were phenotypically similar to Th2 effector cells and were CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high levels of Gata3, Il3, and Il5 Our findings suggest a role of TSLP in directly promoting Th2 cell effector function and support the notion of TSLP as a key driver of Th2 inflammation.


Asunto(s)
Citocinas/inmunología , Células Th2/inmunología , Traslado Adoptivo , Animales , Diferenciación Celular/inmunología , Citocinas/deficiencia , Citocinas/genética , Femenino , Humanos , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores de Interleucina-7/metabolismo , Células Th2/clasificación , Células Th2/citología , Linfopoyetina del Estroma Tímico
5.
J Immunol ; 198(5): 1815-1822, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28115531

RESUMEN

Polymorphisms in genes involved in IL-4 responses segregate with allergic disease risk and correlate with IgE levels in humans, and IL-4 promotes IgE and IgG1 Ab production against allergens in mice. We report that mice with only one intact Il4 gene copy are significantly impaired in their ability to make specific IgE responses against allergens, whereas IgG1 responses to allergens remain unaffected. Il4-hemizygosity also resulted in a modest but detectable drop in IL-4 production by CD4+ T cells isolated from lymph nodes and prevented IgE-dependent oral allergen-induced diarrhea. We conclude that a state of haploinsufficiency for the Il4 gene locus is specifically relevant for IL-4-dependent IgE responses to allergens with the amount of IL-4 produced in the hemizygous condition falling close to the threshold required for switching to IgE production. These results may be relevant for how polymorphisms in genes affecting IL-4 responses influence the risk of IgE-mediated allergic disease in humans.


Asunto(s)
Alérgenos/inmunología , Haploinsuficiencia , Inmunoglobulina E/inmunología , Interleucina-4/genética , Animales , Linfocitos T CD4-Positivos/inmunología , Hipersensibilidad/inmunología , Inmunoglobulina E/biosíntesis , Inmunoglobulina G/inmunología , Interleucina-4/inmunología , Ratones , Polen/inmunología , Polimorfismo Genético
6.
Proc Natl Acad Sci U S A ; 109(37): 14954-9, 2012 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-22930820

RESUMEN

Basophils are powerful mediators of Th2 immunity and are present in increased numbers during allergic inflammation and helminth infection. Despite their ability to potentiate Th2 immunity the mechanisms regulating basophil development remain largely unknown. We have found a unique role for isotype-switched antibodies in promoting helminth-induced basophil production following infection of mice with Heligmosomoides polygyrus bakeri or Nippostrongylus brasiliensis. H. polygyrus bakeri-induced basophil expansion was found to occur within the bone marrow, and to a lesser extent the spleen, and was IL-3 dependent. IL-3 was largely produced by CD4(+)CD49b(+)NK1.1(-) effector T cells at these sites, and required the IL-4Rα chain. However, antibody-deficient mice exhibited defective basophil mobilization despite intact T-cell IL-3 production, and supplementation of mice with immune serum could promote basophilia independently of required IL-4Rα signaling. Helminth-induced eosinophilia was not affected by the deficiency in isotype-switched antibodies, suggesting a direct effect on basophils rather than through priming of Th2 responses. Although normal type 2 immunity occurred in the basopenic mice following primary infection with H. polygyrus bakeri, parasite rejection following challenge infection was impaired. These data reveal a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection.


Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Basófilos/inmunología , Interleucina-3/metabolismo , Nematospiroides dubius/inmunología , Nippostrongylus/inmunología , Infecciones por Strongylida/inmunología , Animales , Cambio de Clase de Inmunoglobulina/inmunología , Interleucina-3/inmunología , Ratones , Ratones Mutantes , Estadísticas no Paramétricas , Células Th2/inmunología
7.
J Immunol ; 186(5): 2719-28, 2011 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-21270410

RESUMEN

IL-4 production by leukocytes is a key regulatory event that occurs early in the type 2 immune response, which induces allergic reactions and mediates expulsion of parasites. CD4(+) T cells and basophils are thought to be the key cell types that produce IL-4 during a type 2 response. In this study, we assessed the relative contribution of both CD4(+) T cell- and basophil-IL-4 production during primary and secondary responses to Nippostrongylus brasiliensis using a murine IL-4-enhanced GFP reporter system. During infection, IL-4-producing basophils were detected systemically, and tissue recruitment occurred independent of IL-4/STAT6 signaling. We observed that basophil recruitment to a tissue environment was required for their full activation. Basophil induction in response to secondary infection exhibited accelerated kinetics in comparison with primary infection. However, total basophil numbers were not enhanced, as predicted by previous models of protective immunity. Overall, the induction and migration of IL-4-producing basophils into peripheral tissues was found to be a prominent characteristic of the primary but not memory responses to N. brasiliensis infection, in which CD4(+) T cells were identified as the major source of IL-4. Whereas basophils were the major initial producers of IL-4, we determined that normal Th2 differentiation occurs independently of basophils, and depletion of basophils led to an enhancement of inflammatory cell recruitment to the site of infection.


Asunto(s)
Basófilos/inmunología , Basófilos/patología , Interleucina-4/biosíntesis , Nippostrongylus/inmunología , Infecciones por Strongylida/inmunología , Infecciones por Strongylida/patología , Animales , Basófilos/metabolismo , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Modelos Animales de Enfermedad , Técnicas de Sustitución del Gen , Memoria Inmunológica/genética , Interleucina-4/genética , Enfermedades Pulmonares Parasitarias/genética , Enfermedades Pulmonares Parasitarias/inmunología , Enfermedades Pulmonares Parasitarias/patología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ratones Transgénicos , Factor de Transcripción STAT6/deficiencia , Factor de Transcripción STAT6/genética , Infecciones por Strongylida/genética , Células Th2/inmunología , Células Th2/metabolismo , Células Th2/patología
8.
J Immunol ; 184(3): 1143-7, 2010 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-20038645

RESUMEN

Basophils are recognized as immune modulators through their ability to produce IL-4, a key cytokine required for Th2 immunity. It has also recently been reported that basophils are transiently recruited into the draining lymph node (LN) after allergen immunization and that the recruited basophils promote the differentiation of naive CD4 T cells into Th2 effector cells. Using IL-3(-/-) and IL-3Rbeta(-/-) mice, we report in this study that the IL-3/IL-3R system is absolutely required to recruit circulating basophils into the draining LN following helminth infection. Unexpectedly, the absence of IL-3 or of basophil LN recruitment played little role in helminth-induced Th2 immune responses. Moreover, basophil depletion in infected mice did not diminish the development of IL-4-producing CD4 T cells. Our results reveal a previously unknown role of IL-3 in recruiting basophils to the LN and demonstrate that basophils are not necessarily associated with the development of Th2 immunity during parasite infection.


Asunto(s)
Basófilos/inmunología , Basófilos/patología , Movimiento Celular/inmunología , Interleucina-3/fisiología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Infecciones por Strongylida/inmunología , Células Th2/inmunología , Animales , Basófilos/parasitología , Movimiento Celular/genética , Técnicas de Sustitución del Gen , Interleucina-3/deficiencia , Interleucina-3/genética , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Nippostrongylus/inmunología , Receptores de Interleucina-3/deficiencia , Receptores de Interleucina-3/genética , Receptores de Interleucina-3/fisiología , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/patología , Células Th2/parasitología
9.
Proc Natl Acad Sci U S A ; 105(34): 12423-8, 2008 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-18719110

RESUMEN

The expression of interleukin-4 (IL-4) is viewed as the hallmark of a Th2 lymphocyte, whereas the subsequent action of IL-4 and IL-13, mediated through the STAT6 signaling pathway, is seen as a prerequisite for the full development of Th2 immune responses to parasites and allergens. G4 mice, whose IL-4 gene locus contains the fluorescent reporter eGFP, were used to quantify the number of Th2 cells that develop during Nippostrongylus brasiliensis- or allergen-induced immune responses under conditions where IL-4 or STAT6 was absent. Here, we show that deletion of IL-4 or STAT6 had little impact on the number or timing of appearance of IL-4-producing Th2 cells. These data indicate that in vivo differentiation of naïve CD4 T cells to Th2 status often occurs independently of IL-4 and STAT6 and that recently described pathways of Th2 cell differentiation may explain how allergens and parasites selectively induce Th2-mediated immunity.


Asunto(s)
Diferenciación Celular , Inmunidad , Interleucina-4/fisiología , Factor de Transcripción STAT6/fisiología , Transducción de Señal , Células Th2/citología , Alérgenos/inmunología , Animales , Ratones , Ratones Mutantes , Nippostrongylus/inmunología , Parásitos/inmunología
10.
J Exp Med ; 200(4): 507-17, 2004 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-15314076

RESUMEN

Using mice in which the eGfp gene replaced the first exon of the Il4 gene (G4 mice), we examined production of interleukin (IL)-4 during infection by the intestinal nematode Nippostrongylus brasiliensis (Nb). Nb infection induced green fluorescent protein (GFP)pos cells that were FcepsilonRIpos, CD49bbright, c-kitneg, and Gr1neg. These cells had lobulated nuclei and granules characteristic of basophils. They were found mainly in the liver and lung, to a lesser degree in the spleen, but not in the lymph nodes. Although some liver basophils from naive mice express GFP, Nb infection enhanced GFP expression and increased the number of tissue basophils. Similar basophil GFP expression was found in infected Stat6-/- mice. Basophils did not increase in number in infected Rag2-/- mice; Rag2-/- mice reconstituted with CD4 T cells allowed significant basophil accumulation, indicating that CD4 T cells can direct both tissue migration of basophils and enhanced IL-4 production. IL-4 production was immunoglobulin independent and only partially dependent on IL-3. Thus, infection with a parasite that induces a "Th2-type response" resulted in accumulation of tissue basophils, and these cells, stimulated by a non-FcR cross-linking mechanism, are a principal source of in vivo IL-4 production.


Asunto(s)
Basófilos/inmunología , Regulación de la Expresión Génica/inmunología , Interleucina-4/inmunología , Ratones/parasitología , Células Th2/inmunología , Trichostrongyloidea/inmunología , Animales , Basófilos/fisiología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/fisiología , Cartilla de ADN , Citometría de Flujo , Proteínas Fluorescentes Verdes , Inmunoglobulina E/inmunología , Interleucina-4/sangre , Interleucina-4/genética , Hígado/inmunología , Hígado/ultraestructura , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Pulmón/inmunología , Pulmón/ultraestructura , Ratones/genética , Ratones/inmunología , Ratones Transgénicos , Microscopía Electrónica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Front Immunol ; 10: 2143, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31552058

RESUMEN

Basophils are granulocytes involved in parasite immunity and allergic diseases, known for their potent secretion of type 2 cytokines. Identifying their functions has proven to be controversial due to their relative rarity and their complex lineage phenotype. Here, we show that the expression of basophils lineage markers CD200R3 and FcεRIα is highly variable in inflammatory settings and hinders basophils identification by flow cytometry across multiple disease states or tissues. Fluorophore-conjugated antibody staining of these lineage markers strongly activates basophil type 2 cytokine expression, and represents a potential bias for coculture or in vivo transfer experiments. The Basoph8 is a mouse model where basophils specifically express a strong fluorescent reporter and the Cre recombinase. Basophils can be identified and FACS sorted unambiguously by their expression of the enhanced yellow fluorescent protein (eYFP) in these mice. We show that the expression of the eYFP is robust in vivo during inflammation, and in vitro on living basophils for at least 72 h, including during the induction of anaphylactoid degranulation. We bred and characterized the Basoph8xiDTR mice, in which basophils specifically express eYFP and the simian diphtheria toxin receptor (DTR). This model enables basophils conditional depletion relatively specifically ex vivo and in vivo during allergic inflammation and their detection as eYFP+ cells. In conclusion, we report underappreciated benefits of the commercially available Basoph8 mice to study basophils function.


Asunto(s)
Basófilos/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Animales , Ratones Endogámicos C57BL , Piel/inmunología
12.
Front Immunol ; 9: 1211, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29910811

RESUMEN

Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4's role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis (Nb) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues. In the lymph node, a CXCR5+PD-1+ T follicular helper (Tfh) and a CXCR5loPD-1lo Th2 subset could be detected that expressed only IL-4AC but no IL-13DR. The number of IL-4AC+ Tfh cells was not affected by IL-4 deficiency whereas the number of IL-4AC+ Th2 cells was significantly reduced. In the non-lymphoid dermal or lung tissues of allergen primed or Nb-infected mice, three strikingly distinct T cell subsets could be detected that were IL-4AC, or IL-4AC/IL-13DR, or IL-13DR CD4. The IL-4- and IL-4/IL-13-expressing subsets were significantly reduced in IL-4-deficient mice, while the numbers of IL-13-expressing CD4 T cells were not affected by IL-4 deficiency indicating that other factors can play a role in directing the development of this Th2 subtype. Taken together, these data indicate that the appearance of IL-4-expressing Tfh cells in the lymph node is not dependent on IL-4 while the appearance of IL-4-expressing Th2 subsets in the lymph node and IL-4, IL-4/IL-13-expressing Th2 subsets in skin and lung tissues of antigen primed mice is significantly IL-4 dependent.


Asunto(s)
Interleucina-13/metabolismo , Interleucina-4/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Piel/inmunología , Piel/metabolismo , Células Th2/inmunología , Células Th2/metabolismo , Alérgenos/inmunología , Animales , Biomarcadores , Expresión Génica , Genotipo , Inmunización , Inmunofenotipificación , Interleucina-13/genética , Interleucina-4/genética , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Ratones , Ratones Noqueados , Ratones Transgénicos , Modelos Biológicos , Pyroglyphidae/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
13.
J Neuroimmunol ; 140(1-2): 61-8, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12864972

RESUMEN

Certain forms of the neuroendocrine hormone preproenkephalin (PPNK) are produced by T cells, B cells and macrophages. This hormone has been shown to be important in regulating a variety of immune responses; however, the basic mechanisms of this regulation are unknown. Here we examine the ability of CD8 and CD4 PPNK-deficient T lymphocytes to proliferate to antigenic and mitogenic stimuli. We found that lymphocyte activation and proliferation to suboptimal concentrations of both anti-CD3 and antigen was reduced in the absence of PPNK. Proliferation could be rescued by increasing antigen or by co-incubation of PPNK-deficient cells with wild-type cells. These data confirm the importance of neuroendocrine hormones such as PPNK in T cell activation and proliferation and provides a potential mechanism for the regulation of T cell responses by PPNK or its peptide derivatives.


Asunto(s)
Encefalinas/deficiencia , Encefalinas/genética , Activación de Linfocitos/genética , Precursores de Proteínas/deficiencia , Precursores de Proteínas/genética , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Antígenos/fisiología , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Antígenos Virales/fisiología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , División Celular/genética , División Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Citocinas/biosíntesis , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Encefalinas/fisiología , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Muromonab-CD3/fisiología , Precursores de Proteínas/fisiología , Receptores de Interleucina-2/antagonistas & inhibidores , Receptores de Interleucina-2/biosíntesis , Subgrupos de Linfocitos T/citología
14.
J Immunol Methods ; 394(1-2): 62-72, 2013 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-23688767

RESUMEN

Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases.


Asunto(s)
Alérgenos/inmunología , Células Th2/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Femenino , Humanos , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Piel/inmunología
15.
Trends Immunol ; 26(5): 242-7, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15866236

RESUMEN

It is often argued that T cell-mediated immunity to secondary infection is dependent on the 'accelerated' responses of memory T cells in lymph nodes. However, new evidence points to a crucial role for effector memory T cells, which are resident in peripheral tissues, in immune protection. These T cells, which reside in peripheral tissues, are not necessarily bound by an anatomical structure and can be present at many sites. Collectively, they represent a third functional tissue of the immune system, uniquely specialized to mediate protective immunity. We propose that the paradigm 'effector lymphoid tissue' needs to be articulated and developed as a focus of new research to describe and understand the unique role this tissue has in protective immunity.


Asunto(s)
Tejido Linfoide/inmunología , Linfocitos T/inmunología , Animales , Antígenos/inmunología , Humanos , Memoria Inmunológica/inmunología , Modelos Inmunológicos
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