RESUMO
This paper demonstrates and characterizes naturally occurring antibodies to interferon (IFN) in human IgG preparations. In vitro neutralization of the antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12 of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta. Frühsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti-tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A was demonstrated only in those IgG preparations found to neutralize the antiviral effect of IFN. Significant correlation between IFN binding and neutralization capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C, lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6. IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG preparations contain variable but significant levels of high-avidity IFN alpha and IFN beta neutralizing antibodies.
Assuntos
Vírus da Encefalomiocardite/efeitos dos fármacos , Imunoglobulina G , Interferon-alfa/imunologia , Interferon beta/imunologia , Interferon gama/imunologia , Anticorpos Monoclonais/farmacologia , Complexo Antígeno-Anticorpo , Ligação Competitiva , Linhagem Celular , Humanos , Fragmentos Fab das Imunoglobulinas/farmacologia , Imunoglobulina G/classificação , Imunoglobulina G/farmacologia , Interferon alfa-2 , Interferon-alfa/farmacologia , Interferon beta/farmacologia , Interferon gama/farmacologia , Interleucina-6/farmacologia , Cinética , Testes de Neutralização , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Células Tumorais CultivadasRESUMO
In this study we have tried to take advantage of the high genetic homology between conserved regions of human T-cell lymphotropic virus (HTLV) types I and II, hoping that a possible retrovirus in patients with cutaneous T-cell lymphoma (CTCL) would have regions with homology to types I/II. DNA was extracted from punch skin biopsies from 21 patients and subjected to the polymerase chain reaction (PCR), using primer sets designed to match conserved regions in the HTLV-I/II genome. The PCR products were subjected to agarose gel electrophoresis with subsequent Southern blotting and hybridization to an HTLV-I probe. No bands of exogenous origin were seen on the agarose gel or by hybridization. If a retrovirus is present in the skin in CTCL patients, it is either not related to HTLV-I/II, present at a copy number below the PCR detection limit, or has been cleared from the skin before the clinical symptoms appear.
Assuntos
DNA Viral/análise , Vírus Linfotrópico T Tipo 1 Humano/genética , Linfoma Cutâneo de Células T/patologia , Reação em Cadeia da Polimerase , Pele/patologia , Sequência de Bases , Biópsia/métodos , Southern Blotting , Humanos , Linfoma Cutâneo de Células T/genética , Dados de Sequência Molecular , Hibridização de Ácido NucleicoRESUMO
The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.
Assuntos
Células Apresentadoras de Antígenos/fisiologia , Irritantes , Neoplasias Cutâneas/imunologia , Pele/imunologia , Administração Cutânea , Adulto , Idoso , Células Apresentadoras de Antígenos/imunologia , Óleo de Cróton/farmacologia , Epiderme/imunologia , Antígenos HLA-DR/imunologia , Humanos , Irritantes/administração & dosagem , Células de Langerhans/citologia , Células de Langerhans/imunologia , Células de Langerhans/fisiologia , Leucócitos/imunologia , Pessoa de Meia-Idade , Pele/citologia , Dodecilsulfato de Sódio/farmacologia , Linfócitos T/imunologia , Fatores de TempoRESUMO
Cutaneous T-cell lymphoma is characterized by infiltration of the skin by activated CD4+ T lymphocytes. The mechanism by which these T lymphocytes achieve and maintain their activated state is unknown. Antigen-specific activation of T lymphocytes is dependent upon antigen-presenting cells which express HLA-DR class II major histocompatibility complex molecules, such as epidermal Langerhans cells. In addition to CD1+DR+ Langerhans cells, cutaneous T-cell lymphoma lesional epidermis contains major histocompatibility complex class II positive non-Langerhans cell populations, including CD1+OKM5+ bone-marrow-derived cells and DR+ keratinocytes. We asked whether any of these epidermal cell populations demonstrate capacity to activate T lymphocytes. Various numbers of epidermal cells from uninvolved and involved cutaneous T-cell lymphoma plaques were therefore used to stimulate autologous CD4+ and CD8+ T lymphocytes in the absence of exogenous antigen. Involved epidermal cells potently induced proliferation of CD4+ T lymphocytes (S.I. +/- SEM = 466 +/- 45). In contrast, uninvolved epidermal cells only induced background levels of proliferation (S.I. +/- SEM = 2 +/- 0.5, N = 8, p less than 0.01). Neither involved nor uninvolved epidermal cells were able directly to activate CD8+ lymphocytes. The capability of involved epidermal cells to activate CD4+ T lymphocytes was dependent upon CD1+DR+ leukocytes and not DR+ keratinocytes, because depletion of either HLA-DR+, CD1+ or HLe1+ epidermal cells totally abrogated the T-lymphocyte proliferation. Interestingly, on a cell per cell basis CD1+DR+ cells obtained from involved skin, demonstrated relative to CD1+DR+ cells from uninvolved skin, enhanced capacity to activate CD4+ T lymphocytes. Furthermore, CD1+OKM5+ cells from involved epidermis stimulated autologous CD4+ T lymphocytes. This indicates that a unique hitherto undescribed CD1+OKM5+ epidermal antigen-presenting cell population may participate in T-lymphocyte activation. These findings provide support for the concept that the epidermal cells in cutaneous T-cell lymphoma patients, particularly the antigen-presenting cells, may contribute significantly to the activation of CD4+ malignant and/or non-malignant inflammatory T lymphocytes within the skin.
Assuntos
Linfoma/imunologia , Neoplasias Cutâneas/imunologia , Células Apresentadoras de Antígenos , Antígenos CD/análise , Linfócitos T CD4-Positivos/imunologia , Antígenos HLA-DR/imunologia , Humanos , Queratinócitos/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Previous studies have suggested that epidermal-derived interleukin-1 is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL); however, the findings are conflicting and studies that combine immunohistochemistry and functional activity have not been performed. We investigated the interleukin-1 level in epidermis of patients with cutaneous T-cell lymphoma using both immunohistochemistry, enzyme-linked immunosorbent assays, and the thymocyte co-stimulation assay. Using supernatants obtained from epidermal cell cultures, we found a significant but small increase of interleukin 1 alpha protein release from involved CTCL epidermis compared to normal epidermis from healthy individuals. Both keratinocytes and leukocytes could release interleukin-1 alpha, but the majority was derived from the keratinocytes. Interleukin-1 beta protein was not detectable. In the thymocyte assay, interleukin-1 alpha was found to be biologically active. When lymphokines derived from a T-cell clone obtained from involved CTCL skin were co-cultured with epidermal cells, an enhanced release of epidermal interleukin-1 alpha could be demonstrated. Because interleukin 1 alpha was increased, we investigated the presence of interleukin 1-inducible keratinocyte-derived interleukin 8 and found it increased in CTCL epidermis compared to normal epidermis from healthy individuals. This study demonstrated an elevated epidermal IL-1 alpha level and IL-8 immunoreactivity in CTCL epidermis, which suggests that this elevated level is induced by lymphokines released from activated T cells.
Assuntos
Interleucina-1/metabolismo , Interleucina-8/metabolismo , Linfoma Cutâneo de Células T/metabolismo , Células Cultivadas , Células Epiteliais , Humanos , Interleucina-1/imunologia , Queratinócitos/metabolismo , Leucócitos/metabolismo , Linfocinas/farmacologia , Pele/químicaRESUMO
Lamins A, B, and C are the major proteins of a polymeric structure called nuclear lamina, which is intercalated between chromatin and the inner membrane of the nuclear envelope. Using immunofluorescence on HEp-2 cells, specific enzyme-linked immunosorbent assay, and Western blotting performed against nuclear lamina preparation from Ehrlich ascites tumor cells, we characterized three patients, whose sera contained antibodies to nuclear lamins. The reaction pattern observed in two of the patients may result from single or combined occurrence of anti-lamin A and C antibodies. The third patient had antibodies that probably recognized an epitope in the carboxy-terminal region of lamin C. The sera were donated by a heterogeneous group of patients, and no common clinical or laboratory signs seemed to link them together.
Assuntos
Autoanticorpos/análise , Lamina Tipo A , Proteínas Nucleares/imunologia , Adulto , Anticorpos Antinucleares , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Immunoblotting , Laminas , Pessoa de Meia-IdadeRESUMO
The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) beta- and gamma-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy.
Assuntos
Linfoma/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Linfócitos T/fisiologia , Divisão Celular , Células Clonais , Rearranjo Gênico , Genótipo , Humanos , Linfoma/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T alfa-beta , Receptores de Antígenos de Linfócitos T gama-delta , Neoplasias Cutâneas/genética , Linfócitos T/patologiaRESUMO
Antigen-dependent activation of T cells occurs through the T-cell antigen-receptor complex (TCR/CD3). Antigen-independent T-cell activation may occur through the surface molecules CDw60, CD2, and CD28. We wished to determine whether these antigen-independent T-cell-activation pathways could be involved in proliferation of leukemic T cells from patients with cutaneous T-cell lymphoma (CTCL). Whereas CDw60 was only expressed on 28% +/- 7% (mean +/- SEM) of blood T cells obtained from healthy control subjects (n = 4), CDw60 was expressed on 94% +/- 3% of blood T cells obtained from patients with CTCL (n = 4). Dual color immunofluorescence microscopy of the T-cell infiltrate in involved skin of these patients demonstrated that almost 100% of the T cells expressed CDw60. Not only did T cells in the patients with CTCL express CDw60, but triggering of the T cells with anti-CDw60 resulted in enhanced proliferation relative to anti-TCR/CD3 and mitogenic lectins. Other antigen-independent pathways also appeared highly active in the T cells from patients with CTCL because enhanced proliferation relative to anti-TCR/CD3 or mitogenic lectins was found when anti-CD2 or anti-CD28 plus phorbol ester was used as stimulant. Despite the brisk proliferation induced by anti-CDw60, anti-CD2, or anti-CD28, T cells from the patients did not produce detectable amounts of gamma-interferon. The inability to produce gamma-interferon correlates with our finding of absent (n = 3) or weak (n = 1) intercellular adhesion molecule-1 expression in the lesional keratinocytes in these patients. In conclusion, T cells of patients with CTCL demonstrate elevated expression of a T-cell-independent signaling molecule CDw60 and respond to antigen-independent activating signals.
Assuntos
Leucemia/patologia , Ativação Linfocitária , Linfoma de Células T/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T/patologia , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos CD2 , Antígenos CD28 , Humanos , Interferon gama/metabolismo , Linfoma de Células T/metabolismo , Pessoa de Meia-Idade , Receptores Imunológicos/imunologia , Neoplasias Cutâneas/metabolismo , Linfócitos T/metabolismoRESUMO
We measured sICAM-1 in paired samples of serum and cerebrospinal fluid (CSF) from patients with an attack of multiple sclerosis (MS) (n = 50) and patients with acute monosymptomatic optic neuritis (ON) as a possible first attack of MS were also included (n = 25). Based on calculations of extended indices we found evidence of intrathecal synthesis of sICAM-1 both in patients with clinically definite MS and in patients with idiopathic ON compared to neurological control subjects. The amount of intrathecally synthesized sICAM-1 correlated significantly to the CSF leukocyte count and to the concentration of myelin basic protein in the CSF. The serum concentrations of sICAM-1 were not increased in patients with demyelinating disease compared to the neurological control subjects.
Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Bainha de Mielina/metabolismo , Neurite Óptica/metabolismo , Neurite Óptica/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/patologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Proteína Básica da Mielina/líquido cefalorraquidiano , Concentração Osmolar , Análise de Regressão , Albumina Sérica/líquido cefalorraquidiano , Solubilidade , Medula Espinal/metabolismoRESUMO
Current understanding of the immunological mechanisms involved in the pathogenesis of venous leg ulcers is insufficient. In this study the cellular composition of skin biopsies taken from the center, the edge, and 2 cm distant from the edge of venous leg ulcers was characterized quantitatively by immunohistochemical staining. In the epidermis the mean numbers of Langerhans cells (CD1a+) were four times lower at the edge of the ulcer compared to clinically intact epidermis 2 cm distant from the edge. In the dermis a statistically significant increase in the mean numbers of macrophages (CD68+) and neutrophils (NP57+) from the distant area towards the center of the ulcer was observed. No significant differences were observed in the distribution of T cells nor in the ratio of CD4+/CD8+ T-cell subsets between the different regions of the ulcer. About 30% of T lymphocytes were CD8+ in all microenvironments. The center and the edge of the ulcer were dominated by macrophages comprising 63% and 53% of the cells respectively, while T lymphocytes dominated the distant area. The area 2 cm distant from the edge was also heavily infiltrated by macrophages and neutrophils. B cells (CD22+) and NK cells (CD56+) were relatively rare in all areas, comprising less than 3% of the dermal infiltrate. In conclusion, local microenvironments each with a different cellular composition can be defined within venous leg ulcers.
Assuntos
Células de Langerhans , Linfócitos , Macrófagos , Neutrófilos , Pele/imunologia , Úlcera Varicosa/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B , Contagem de Células , Doença Crônica , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Células Matadoras Naturais , Contagem de Leucócitos , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos TRESUMO
Human papillomavirus-induced infections may be associated with cellular immunodeficiency. However, very little is known about the dysfunctional interactions among T lymphocytes, B lymphocytes, and antigen-presenting cells. A 30-year-old heterosexual man with a 10-year history of persistent multiple refractory flat wart lesions containing human papillomavirus type 3-related DNA sequence was studied. The patient had a severe depletion of CD4+ T lymphocytes and a compensatory increase in the number of CD8+ T lymphocytes. Impaired T-lymphocyte response to various stimuli was found. Depletion of the increased number of CD8+ T lymphocytes, which suppressed immunoglobulin production in vitro, did not restore the impaired T-lymphocyte response. Immobilized anti-CD3 beads that stimulate the T lymphocyte antigen complex in the absence of antigen-presenting cells indicated a T-lymphocyte defect, rather than a decreased antigen-presenting cell function. Thus, the pronounced cellular immunodeficiency was due to abnormal function of the CD4+ helper/inducer T lymphocytes.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Papillomaviridae/imunologia , Infecções Tumorais por Vírus/imunologia , Adulto , Linfócitos B/imunologia , DNA Viral/análise , Humanos , Imunoglobulina G/biossíntese , Contagem de Leucócitos , Masculino , Papillomaviridae/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
The mortality rate of nonmelanoma skin cancer is higher than generally considered. An actual nonmelanoma skin cancer is a risk factor not only for other skin cancers but also for cancers in other organs. The recurrence rate can, according to the method of calculation, yield surprisingly diverging results. Statistical mapping of subclinical tumor growth in basal cell carcinoma supplies the margins for tumor-free excision. An even better but more expensive tool for therapy planning is tumor imaging with magnetic resonance imaging. Psoralen plus ultraviolet light of the A wavelength-treated patients run a dose-dependent risk of developing squamous cell carcinoma of the skin but also cancers in other organs. Human papilloma virus-16 seems not to be associated with squamous cell carcinoma of the skin except for the anogenital region and possibly the finger. The finding of retroviruslike particles in endemic non-acquired immunodeficiency syndrome Kaposi's sarcoma strongly suggests that a virus other than human immunodeficiency virus may play a role in the pathogenesis of this disease.
Assuntos
Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/diagnóstico , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Humanos , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/terapia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/terapiaRESUMO
Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.
Assuntos
Anticorpos Monoclonais , Biomarcadores Tumorais/imunologia , Linfoma Cutâneo de Células T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Neoplasias Cutâneas/imunologia , Humanos , Técnicas Imunoenzimáticas , Linfoma Cutâneo de Células T/diagnóstico , Dermatopatias/imunologiaRESUMO
The presence of intercellular adhesion molecule-I (ICAM-I) on keratinocytes of psoriatic skin lesions before and during 8-methoxapsoralen and UVA light (PUVA) treatment was studied. ICAM-I was expressed on the keratinocytes in biopsies of the skin lesions of five patients with psoriasis. The patients who responded to PUVA treatment had a concurrent reduction of ICAM-I expression on the keratinocytes with a reduction of the number of cells in the mononuclear cellular infiltrate and a lessening of the severity of the disease. Patients who went into remission during therapy and then relapsed showed an increase in ICAM-I expression on keratinocytes with an increase in the number of cells in the mononuclear cell infiltrate and an increase in the severity of the disease. HLA-DR expression on keratinocytes was variable during treatment and showed no strong correlation with disease severity.
Assuntos
Antígenos de Superfície/análise , Epiderme/imunologia , Queratinas , Psoríase/imunologia , Moléculas de Adesão Celular , Epiderme/patologia , Antígenos HLA-DR/análise , Humanos , Terapia PUVA , Psoríase/tratamento farmacológico , Fatores de TempoRESUMO
Biopsies from normal skin (n = 17) and various cutaneous disorders (n = 83) were examined immunohistologically for reactivity with an antibody (CD29) against the common beta chain of the VLA integrin family. In normal skin, CD29 recognized a number of cell types, i.e. endothelial cells, fibroblasts, T lymphocytes and basal keratinocytes. Similar cells were positive in diseased skin, but the expression of VLA beta was upregulated on keratinocytes. The phenotype of the VLA beta-positive T cells was examined in more detail by staining with anti-T-cell antibodies, i.e. CD3, CD4, CD8, CD45RO (UCHL1) and CD45R (2H4). These studies showed that most of the T cells in normal skin, benign cutaneous conditions and early cutaneous T-cell lymphomas (CTCL) expressed a similar phenotype and resembled antigen committed 'memory' (helper/inducer) cells (CD4+, CD29+, CD45RO+, CD45R-). In advanced CTCL, expression of these antigens was more variable, and many of these infiltrates showed aberrant (or unusual) expression of CD29, CD45RO, CD45R and other T-cell antigens. It is concluded that several cells involved in cutaneous immune reactions express a molecule (VLA beta) which acts as a receptor for extracellular matrix components. This molecule is important for the attachment of cells to connective tissue constituents and may act to facilitate the migration of lymphocytes (and other cells) during immune reactions in normal and diseased cutaneous conditions. Advanced CTCL differ from the early lesions and it is possible that there is a progressive accumulation of increasingly malignant (or transformed) cells in these conditions.
Assuntos
Linfoma Cutâneo de Células T/imunologia , Receptores de Antígeno muito Tardio/análise , Dermatopatias/imunologia , Neoplasias Cutâneas/imunologia , Pele/imunologia , Antígenos CD/análise , Antígenos de Diferenciação/análise , Antígenos de Histocompatibilidade/análise , Humanos , Imuno-Histoquímica , Integrina beta1 , Antígenos Comuns de Leucócito , Líquen Plano/imunologia , Micose Fungoide/imunologia , Fenótipo , Linfócitos T/imunologiaRESUMO
In this report we have reviewed studies on the clinical effect of the interferon (IFN) treatment of 304 patients suffering from cutaneous T-cell lymphoma (CTCL). Intramuscular, subcutaneous or intralesional administration of recombinant IFN has been used as monotherapy or as part of combination therapy. In general, IFN has proved to be a relatively effective agent in the treatment of CTCL, and the best responses have been achieved in the early stages of the disease. In CTCL the overall response rate to IFN including complete, partial and minor responses is 70%. Neither the doses nor the routes of administration in these studies has any statistically significant influence on the clinical response to IFN treatment. Continuous low-dose IFN therapy, presumably in combination with psoralen and UVA light (PUVA), is recommended. This review concludes that the clinical stage of disease before treatment is the only known predictive parameter concerning the clinical response to IFN treatment in patients with CTCL.
Assuntos
Interferons/uso terapêutico , Linfoma Cutâneo de Células T/terapia , Terapia Combinada , Humanos , Interferon Tipo I/uso terapêutico , Interferons/administração & dosagem , Terapia PUVA , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêuticoRESUMO
Forty-one patients with lymphomatoid papulosis have been followed from 1 to 22 years (mean 11.4 years, median 10 years). Six patients developed malignant lymphoma, 3 cutaneous T-cell lymphoma, 2 Ki-1 large cell lymphoma, and 1 Hodgkin's disease. A clinical malignant presentation combined with the finding of aneuploidy in skin lesions seem to be indications of a malignant potential. Treatment with methotrexate in low dosage is an efficient treatment of lymphomatoid papulosis and probably diminishes the risk of malignancy.
Assuntos
Papulose Linfomatoide , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Doença de Hodgkin/etiologia , Humanos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Cutâneo de Células T/etiologia , Papulose Linfomatoide/diagnóstico , Papulose Linfomatoide/fisiopatologia , Papulose Linfomatoide/terapia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Terapia PUVARESUMO
Examination of biopsy samples from 62 patients with--or with suspected--cutaneous T-cell lymphoma (CTCL) revealed 2 cases in which the neoplastic cells were positive for the T-cell receptor (TCR) gamma delta complex. One patient had mycosis fungoides and 1 patient had a pleomorphic lymphoma of medium and large-cell type. Both cases showed aggressive courses with dissemination to internal organs and short survival times. The phenotypic examination showed that the neoplastic cells were positive with TCR delta 1, CD3, CD25, CD29, CD45R0 and CD54. No staining was seen with antibodies against framework determinants or variable regions on the TCR alpha beta heterodimer. Negative reactions were also seen with CD4, CD8, CD5, CD7, CD16, CD30 and CD57. It is concluded that rare CTCL express TCR gamma delta chains. These malignancies may originate from the TCR gamma delta-positive T cells seen in normal skin, and it is possible that their recognition may be important for clinical reasons.
Assuntos
Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Neoplasias Cutâneas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologiaRESUMO
Subcutaneous insertion of expanded polytetrafluoroethylene tubes with local anesthesia constitutes a minimally invasive model permitting quantitative and qualitative studies of the wound healing potential in human beings. Light and electron microscopic examination of these implants in rats showed a normally appearing granulation tissue. The amount of hydroxyproline accumulated in the expanded polytetrafluoroethylene tubes may be assayed and converted to collagen content. In 28 surgical patients, the collagen content increased from 6.6 microg/cm (interquartile range: 5.1 to 9.9) after 5 days to 12.4 microg/cm (7.1 to 16.8) after 10 days (p < 0.05). The median ratio between the higher and lower collagen amount measured in two expanded polytetrafluoroethylene tubes inserted for an identical period within the same patient was 1.25 (1.10 to 1.81). This variability ratio was not related to the amount of collagen accumulated or the duration of implantation. There was a tendency for higher collagen amounts in the middle section than in the ends of the expanded polytetrafluoroethylene tubes, with a median ratio between the two sections equaling 1.12 (0.96 to 1.58); (p > 0.05). No infectious or hemorrhagic complications from the insertion occurred in any of the patients. Increments of collagen deposition with time may be easily assessed by this expanded polytetrafluoroethylene tube model, which is inexpensive and has high patient acceptance. Measurement variability was encountered, which has to be taken into account when designing clinical trials.