02421nas a2200361   4500000000100000008004100001260001300042653002700055653002300082653003100105653001800136653001600154653001400170653002000184653002400204653001100228653001200239653002500251653003100276653002600307653001400333653001400347100001400361700001700375700001300392700002200405700001400427245010600441300000900547490000700556520148200563022001402045       1997                            d  c1997 Jan10aAdjuvants, Immunologic10aBacterial Proteins10aCD4-Positive T-Lymphocytes10aChaperonin 6010aChaperonins10aCytokines10aHLA-DR Antigens10aHeat-Shock Proteins10aHumans10aleprosy10aMycobacterium leprae10aMycobacterium tuberculosis10aPolymorphism, Genetic10aTh1 Cells10aTh2 Cells1 aMitra D K1 aRajalingam R1 aTaneja V1 aBhattacharyya B C1 aMehra N K00aHLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP-reactive CD4+ T cells.  a60-70 v823 a<p>In the present study, in vitro attempts have been made to define the cytokine profile of CD4+ T cells from polar leprosy patients and healthy individuals against Mycobacterium leprae-derived heat shock proteins (HSPs), HSP65 and HSP18, and their trypsin-digested fragments, relating to HLA-DR polymorphism. While all tryptic fragments of optimal digestion and undigested HSPs could stimulate CD4+ T cells from tuberculoid (TT) leprosy patients and healthy contacts (stimulation index, SI > 2.0), only two fragments, TDB65-2 (18 kDa) and TDB18-3 (3 kDa) triggered CD4+ T cells of anergic lepromatous (LL) leprosy patients. Both of these HSPs and their tryptic fragments showed diverse HLA-DR restriction, with DR15 providing the strongest restriction. Cytokine analysis demonstrated that HSP65 and HSP18 induced Th1-like activity in the context of all the restricting HLA-DR alleles, except DR1 and DR7 which induced a Th2 type of response against HSP65 and HSP18, respectively. These Th2 inducer epitopes on HSP65 (DR1 restricted) and HSP18 (DR7 restricted) were absent from TDB65-2 and TDB18-3 which exclusively triggered Th1 cells in both TT and LL forms of leprosy in the context of multiple DR alleles, DR15 being the major antigen-presenting allele. These studies suggest that the major histocompatibility complex phenotype of the antigen-presenting cell can modulate Th1-like versus Th2-like activity against M. leprae pathogens in leprosy and healthy individuals.</p>  a0090-1229