HLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP-reactive CD4+ T cells.
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.
Mitra
D K
DK
Histocompatibility and Immunogenetics Department, All India Institute of Medical Sciences, New Delhi.
Rajalingam
R
R
Taneja
V
V
Bhattacharyya
B C
BC
Mehra
N K
NK
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007918:Leprosy / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology; D009169:Mycobacterium tuberculosis; D011110:Polymorphism, Genetic; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; C074119:heat-shock protein 65, Mycobacterium; C081475:hsp18 protein, bacteria; D018833:Chaperonins