Characterization of the HLA class I genotypes of a Venezuelan Amerindian group by molecular methods.

We have characterized the HLA class I genotypes of the Yucpa, a tribe of Venezuelan Amerindians, using molecular methods. The study was carried out on DNA extracted from unrelated individuals using low resolution ARMS-SSP typing with sequence-specific primers, high resolution typing using reference strand conformation analysis (RSCA), and for some samples sequence-based typing (SBT). The following class I alleles were found to be present in this tribe: for the HLA-A locus A*0204, A*0212, A*0213, A*2402, A*3101 and A*6801; for the B locus B*1522, B*3512, B*3905, B*3909, B*4004 and B*52012, and for C locus Cw*0102, Cw*0302/ 4, Cw*0401, Cw*0702 and Cw*1503. This is the first time these alleles have been described in this group, although all of them have previously been reported as being present in other Amerindian tribes. The study confirmed the high frequency of HLA-B39 which was previously observed in serological analysis of this tribe, and indicated that two different B*39 alleles were present in this population. The identification of the class I alleles by molecular methods for this ethnic group confirms the restricted polymorphism of the MHC molecules previously obtained by serology and has allowed a more accurate definition of the different alleles present in this population.

Activation of human tonsil lymphocytes by rabies virus nucleocapsid superantigen.

The capacity of the rabies virus superantigen (SAg) and the nucleocapsid (NC) to activate human tonsil lymphocytes was analyzed by studying the capacity of NC to cause lymphocytes to proliferate and secrete Ig and cytokines. NC activation was compared to that obtained with the Staphylococcus-derived SAg, SEE, and TSST-1. Despite a weak T lymphocyte mitogenic activity restricted to CD4+ T cells, NC triggers tonsil B lymphocytes to produce IgG in quantities and frequencies similar to those of SEE and TSST-1. In the same way as these two SAg, NC induces IgG production only in the presence of T cells and optimally with a T/B ratio of 1/5. However, unlike SEE and TSST-1, NC does not trigger IgM production. The pattern of cytokines produced upon NC activation, IL-4 and IL-10, weak IL-2 production, and no IFN-gamma, suggests that rabies SAg stimulates Th2 rather than Th1 lymphocytes. In contrast, the pattern of cytokines produced upon TSST-1 activation, IL-2, IFN-gamma, and no IL-4, suggests that TSST-1 induces rather a Th1 response. The specific Th2 triggering by NC could explain the unique capacity of the rabies SAg to increase the in vivo antibody response to a simultaneously injected antigen.

Evidence for a viral superantigen in humans.

Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-encoded self-superantigens induce clonal deletion of T lymphocytes. Although superantigen-like properties have been suggested for human immunodeficiency virus-1, no viral superantigen has been identified in humans. Here we report that the nucleocapsid of the rabies virus is an exogenous superantigen specific for V beta 8 human T lymphocytes which binds to HLA class II alpha-chains.

Immunocytochemical characterization of immune cells in lesions of American cutaneous leishmaniasis using novel T cell markers.

Some recently defined lymphocyte immunophenotypes were determined in lesions of patients with American cutaneous leishmaniasis (ACL). New monoclonal antibodies have allowed the demonstration of cell surface antigens of T lymphocytes, such as CD45RA and CD45RO, which recognize different maturational stages of the same T CD4+ cell subgroup: 'virgin' (CD4+CD45RA+) and 'memory' (CD4+CD45RO+) T cells respectively. The CD4/CD8 cell ratios were higher in mucocutaneous leishmaniasis (MCL) than in localized cutaneous leishmaniasis (LCL) lesions. Diffuse cutaneous leishmaniasis (DCL) has the highest values of 'virgin' T cells; LCL and MCL patients have lower values, similar to each other. 'Memory' T cells were higher in MCL than in LCL or DCL. The ratio of 'memory'/'virgin' T cells was 7.9 for LCL, 9.6 for MCL and 2.5 for DCL. The highest value for IL-2 receptor positive cells (CD25) was observed in LCL, whereas single CD45RO-immunoreactive cells showed a peak value in DCL patients. HLA-DR+ cells were present in all three clinical forms of ACL. MCL patients showed a lack of epithelial Langerhans cell (CD1a+) in the nasal mucosa.

Linfocitos T vírgenes y T memoria en la leishmaniasis cutánea americana / Tlyphovytes virgins and TY memory in American cutaneous leishmaniasis

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