Immunosuppression in hamsters with progressive visceral leishmaniasis: an evaluation of the role of nitric oxide toward impairment of the lymphoproliferative response

The progressive visceral infection caused in golden hamsters by Leishmania donovani amastigotes led to gradual impairment of the proliferative respons e of their splenic (SPMC) or peripheral blood (PBMC) mononuclear cells to i n vitro stimulation with leishmanial antigen, with mitogen (concanavalin A) , and even with a combination of phorbol myristate acetate (PMA) and ionomy cin (Io). Removal of macrophage-like adherent cells from SPMC or PBMC of in fected animals, however, almost completely restored their proliferative res ponse to PMA + Io, thus ruling out the possibility of any intrinsic defect in the signal-transduction pathways of lymphocyte activation and proliferat ion. Subsequent studies demonstrated that the generation of soluble mediato rs such as nitric oxide by these adherent cells is responsible, albeit part ially, for the down-regulation of the lymphoproliferative response in hamst ers with visceral leishmaniasis.