02721nas a2200385 4500000000100000008004100001260001300042653002900055653001700084653001700101653001700118653002000135653002000155653001100175653001700186653001900203653001900222653001200241653002700253653001400280653002500294653001800319100001500337700001500352700001600367700001300383700001400396700001300410700002100423245012500444300001000569490000700579520173500586022001402321 2001 d c2001 Feb10aAntigen-Presenting Cells10aAntigens, CD10aB7-1 Antigen10aB7-2 Antigen10aCells, Cultured10aDendritic Cells10aHumans10aImmunization10aInterleukin-1010aInterleukin-1210aleprosy10aMembrane Glycoproteins10aMonocytes10aMycobacterium leprae10aT-Lymphocytes1 aSantos D O1 aSantos S L1 aEsquenazi D1 aNery J A1 aDefruyt M1 aLorré K1 aVan Heuverswyn H00aEvaluation of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules and dendritic cells on the immune response in leprosy. a15-240 v703 a

The cell activation depends on T cell antigen receptor binding to antigen plus MHC and costimulation. The binding of CD28, expressed on the T cell surface to B7 (B7-1 or CD80/B7-2 or CD86) present on the antigen--presenting cells (APCs), determines, in several T cell function models, if activation or anergy follows antigenic stimulation. In leprosy, the role of CD80 and CD86 as costimulatory signal in M. leprae-specific cellular immunity has not yet been defined. We investigated the role of B7-CD28 pathway of T cell activation in the in vitro response to M. leprae, following stimulation in the presence of monocytes or dendritic cells (DCs) as APCs. Monocytes were purified, by cold aggregation, from peripheral blood mononuclear leukocytes (PBMC), isolated from leprosy patients. In order to obtain DCs, the monocytes were cultured in the presence of IL-4 and GM-CSF. T cells were purified from PBMC by negative selection with mABs and C'. The phenotype of the cell populations was monitored by FACS. Lymphoproliferative assays were performed with T cells, in the presence of monocytes or DCs. The cells were stimulated by M. leprae in the presence of anti-CD80 antibody (Ab) and/or anti-CD86 antibody (Ab) (Innogenetics). In some experiments Il-10, Il-12 and anti-Il-12 Ab were also added to the culture. We observed a significantly more efficient APC function for DCs when compared to monocytes in T cell in vitro responses to M. leprae. Regardless of the clinical form of Leprosy, the M. leprae-specific immune response was markedly reduced in the presence of anti-CD86 Ab. Il-12 increase the immune response to M. leprae while IL-10 or anti-IL-12 Ab reduce this response when monocytes or DCs were used as APCs.

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