Immunological unresponsiveness in leprosy and its relevance to immunoregulation in man.
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Date
1984-12
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Abstract
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 of
Mycobacterium leprae. Even though all currently known protein species of Mycobacterium
leprae and BCG are cross-reactive, lepromatous patients unreactive to Mycobacterium leprae
antigens frequently respond strongly to tuberculin. In vitro experiments suggest the existence
of lepromin-induced suppressor activity, mediated by both monocytes and Τ cells. The Τ
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 the Ts cells largely recognize the terminal trisaccharide of this unique antigen.
Depletion of Ts cells restores in vitro reactivity of lymphocytes to lepromin in a portion of
lepromatous patients, and addition of IL-2 containing supernatants partially restores
responsiveness to Mycobacterium leprae antigens. Vaccination of lepromatous patients with a
mixture of Mycobacterium leprae and live BCG restores cell-mediated immunity in the
majority of lepromatous patients, and concomitantly reduces the in 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 of TH capable of responding to either specific
or cross-reactive mycobacterial antigens. The mode of action of these Ts 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.
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Keywords
Leprosy-immunology-unresponsiveness, lepromin-induced Τ suppressor cells, phenolic glycolipid, interleukin-2, gamma-interferon, immunoprophylaxis
Citation
Bloom Barry R, Mehra Vijay. Immunological unresponsiveness in leprosy and its relevance to immunoregulation in man. Journal of Biosciences. 1984 Dec; 6(5): 665-683.