The varied forms of leprosy form a clinical and immunological spectrum which offers extraordinary possibilities for insight into immunoregulatory mechanisms in man. At one pole, tuberculoid leprosy, patients develop high levels of cell-mediated immunity which ultimately results in killing of bacilli in the tissues, albeit often with damage to nerves. At the lepromatous pole, patients exhibit selective immunological unresponsiveness to antigens ofMycobacterium leprae. Even though all currently known protein species ofMycobacterium leprae and BCG are cross-reactive, lepromatous patients unreactive toMycobacterium leprae antigens frequently respond strongly to tuberculin.In vitro experiments suggest the existence of lepromin-induced suppressor activity, mediated by both monocytes andT cells. TheT suppressor cells have the T8 phenotype of which 50% express the activation markers,Ia and FcR. The one unique species of antigen of the leprosy bacillus is a phenolic glycolipid, and it appears that theTs cells largely recognize the terminal trisaccharide of this unique antigen. Depletion ofTs cells restoresin vitro reactivity of lymphocytes to lepromin in a portion of lepromatous patients, and addition of IL-2 containing supernatants partially restores responsiveness toMycobacterium leprae antigens. Vaccination of lepromatous patients with a mixture ofMycobacterium leprae and live BCG restores cell-mediated immunity in the majority of lepromatous patients, and concomitantly reduces thein vitro suppressor activity and number of activated T8 cells.
These experiments suggest the existence of stage-of-disease related suppressor cells in leprosy which appear to block the responsiveness ofTH capable of responding to either specific or cross-reactive mycobacterial antigens. The mode of action of theseTs appears to be the inhibition of production of IL-2 and other lymphokines. Successful immunotherapeutic vaccination appears to overcome this block in the majority of patients.
Volume 44 | Issue 5
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