ABSTRACT
Interactions between immunocompetent cells require the participation of T cell antigen receptor (TCR) and the integrin lymphocyte function-associated molecule-1 (LFA-1, CD11a/CD18). These interactions are mediated by interlinking cytokines, which are important in determining the type of immune response. In the present study, we have shown that in American cutaneous leishmaniasis (ACL) lesions, most infiltrating T cells expressed the alpha beta TCR including those selectively migrating to the epidermis. In contrast, gamma delta T cells were abundant in localized (LCL) and scarce in muco-cutaneous (MCL) and diffuse (DCL) cutaneous leishmaniasis, suggesting a role in effective granulomas. There were differences in the expression of LFA-1 alpha and beta subunits, with most cells expressing LFA-1 beta. The ratio LFA-1 beta/LFA-1 alpha was higher in LCL (11.8:1) than in MCL (3.3:1) and DCL (2.4:1). Similar results were observed in Leishmania mexicana-infected C57BL/6 mice. DCL lesions showed a higher proportion of LFA-1 alpha+ cells than MCL and LCL lesions. A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of the cytokine profiles showed that most T cells present in the MCL and DCL lesions secrete a mixture of Type 1 and Type 2 cytokine patterns, but in DCL granulomas predominate the Type 2 cytokines. In LCL the cytokine patterns show a preponderance of INF gamma over IL-4, and low levels of IL-5 and IL-10, suggesting a Type 1 cytokine profile
Subject(s)
Animals , Female , Humans , Mice , Leishmaniasis, Cutaneous/immunology , Lymphokines/biosynthesis , Skin/immunology , T-Lymphocyte Subsets/immunology , Antibodies, Monoclonal , Cell Adhesion Molecules/biosynthesis , Granuloma/immunology , Leishmaniasis, Diffuse Cutaneous/immunology , Leishmaniasis, Mucocutaneous/immunology , Lymphocyte Function-Associated Antigen-1/biosynthesis , Lymphokines/immunology , Mice, Inbred C57BL , Polymerase Chain Reaction , Receptors, Antigen, T-Cell/biosynthesis , RNA-Directed DNA Polymerase , T-Lymphocytes/immunologyABSTRACT
La caracterización in situ de subpoblaciones leucocitarias ha permitido evaluar la participación de los diferentes componentes celulares en la respuesta inmunológica a distintos agentes patógenos. En lesiones de leishmaniasis cutánea americana se ha podido demostrar que parte de la falla inmunológica de los pacientes con leishmaniasis difusa recae sobre la subpoblación de lifocitos cooperadores inductores CD4+, los cuales no son capaces de producir Interleucina-2. Nuevos anticuerpos monoclonales permiten subdividir a los linfocitos T CD4+ en linfocitos T vírgenes CD4+ CD45RA+ y linfocitos T memoria CD4+CD45RA. En el presente estudio, se demostró que el número de linfocitos T memoria es mayor en pacientes muco-cutáneos (LCM) que localizados (LCL) y difusos (LCD). La relación de linfocitos T memoria/T vírgenes fue de 7,9 para LCM y 2,5 para LCD. Esta relación es una nueva forma de evaluar la condición inmunológica de los individuos, y pudiera ser útil en la evaluación de esquemas terapéuticos