CUTANEOUS LEISHMANIASIS IN ANTI-IGM-TREATED MICE - ENHANCED RESISTANCE DUE TO FUNCTIONAL DEPLETION OF A B-CELL-DEPENDENT T-CELL INVOLVED IN THE SUPPRESSOR PATHWAY

Abstract

The contribution of B cells and antibodies to either the resistance or susceptibility to cutaneous leishmaniasis has been investigated in mouse strains rendered B cell-deficient by treatment with anti-mouse IgM antisera from birth (.mu.-suppressed). These studies confirm that immunity to cutaneous disease in a normally resistant mouse strain (C3H/HeJ) is independent of antibody, but that B cells and/or antibodies are required for the evolution of suppressed DTH [delayed type hypersensitivity] and the consequent disease susceptibility of BALB/c mice. Anti-IgM-treated BALB/c mice, which lacked detectable antileishmanial antibodies during the course of infection, displayed a sustained DTH response to leishmanial antigen and were able to control their cutaneous lesions. The enhanced resistance of .mu.-suppressed mice could be completely abrogated by transfer of suppressor T cells from infected control animals into .mu.-suppressed mice before their infection. The suppressor T cells, which are generated during leishmanial infection in BALB/c mice, can effect suppression in the absence of antibody. Apparently, B cells or antibodies are required for the generation of suppressor T cells was demonstrated by using BALB/c mice in which suppressor T cells fail to be generated during infection as a result of prior sublethal irradiation. Splenic T cells from normal mice could overcome the resistance conferred by sublethal irradiation, whereas splenic T cells from .mu.-suppressed mice could not. Thus, the enhanced resistance of .mu.-suppressed BALB/c mice appears to be a consequence of their lack of functional expression of a B cell-dependent T cell critical to the suppressor pathway.