Mechanisms of T-cell unresponsiveness in leprosy.
We analysed the mechanisms of T-cell unresponsiveness to Mycobacterium leprae antigens and to unrelated antigens or T-cell mitogens in human leprosy and in an experimental model of murine infection by M. lepraemurium (MLM). In human leprosy, monoclonal antibodies OKT3, OKT4 and OKT8 were used to enumerate T-cell subpopulations within peripheral blood. Increased percentages of OKT8+ cytotoxic/suppressor cells were observed in untreated, non-reactional lepromatous patients. Conversely, lepromatous patients suffering from erythema nodosum leprosum, an Arthus-like phenomenon, exhibited a transient drop in the percentage of OKT8+ cells with a correlative increase in the proliferative response to T-cell mitogens. We studied the proliferative response to M. leprae of OKT4+ and OKT8+ cells isolated by a negative selection procedure using antibody-induced cytotoxicity plus complement. None of these subpopulations proliferated when incubated with M. leprae. In some patients, control treatment of mononuclear cells with complement alone induced the reappearance of a strong proliferative response to M. leprae, suggesting the existence of an active suppressor mechanism through soluble factors of an unknown nature. In MLM-induced murine leprosy, a progressive decrease was observed in the proliferative response to concanavalin A (ConA), and an early decrease in interleukin 2 activity in supernatants from ConA-stimulated spleen cells. Splenic T cells from MLM-infected mice transferred into naive recipients accelerated the local MLM growth in these recipients, suggesting that suppressor T cells may play a pathogenic role in the progression of MLM infection.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D007376:Interleukin-2; D014373:Tuberculin; D003208:Concanavalin A