HLA-DR POLYMORPHISM MODULATES THE CYTOKINE PROFILE OF MYCOBACTERIUM-LEPRAE HSP-REACTIVE CD4(-CELLS() T)

In the present study, in vitro attempts have been made to define the c ytokine profile of CD4(+) T cells from polar leprosy patients and heal thy individuals against Mycobacterium leprae-derived heat shock protei ns (HSPs), HSP65 and HSP18, and their trypsin-digested fragments, rela ting to HLA-DR polymorphism. While all tryptic fragments of optimal di gestion and undigested HSPs could stimulate CD4(+) T cells from tuberc uloid (TT) leprosy patients and healthy contacts (stimulation index, S I > 2.0), only two fragments, TDB65-2 (18 kDa) and TDB18-3 (3 kDa) tri ggered CD4(+) T cells of anergic lepromatous (LL) leprosy patients. Bo th of these HSPs and their tryptic fragments showed diverse HLA-DR res triction, with DR15 providing the strongest restriction, Cytokine anal ysis demonstrated that HSP65 and HSP18 induced Th1-like activity in th e context of all the restricting HLA-DR alleles, except DR1 and DR7 wh ich induced a Th2 type of response against HSP65 and HSP18, respective ly. These Th2 inducer epitopes on HSP65 (DR1 restricted) and HSP18 (DR 7 restricted) were absent from TDB65-2 and TDB18-3 which exclusively t riggered Th1 cells in both TT and LL forms of leprosy in the context o f multiple DR alleles, DR15 being the major antigen-presenting allele. These studies suggest that the major histocompatibility complex pheno type of the antigen-presenting cell can modulate Th1-like versus Th2-l ike activity against M. leprae pathogens in leprosy and healthy indivi duals. (C) 1997 Academic Press, Inc.