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 response of their splenic (SPMC) or peripheral blood (PBMC) mononuclear cells to in vitro stimulation with leishmanial antigen, with mitogen (concanavalin A), and even with a combination of phorbol myristate acetate (PMA) and ionomycin (Io). Removal of macrophage-like adherent cells from SPMC or PBMC of infected animals, however, almost completely restored their proliferative response to PMA + Io, thus ruling out the possibility of any intrinsic defect in the signal-transduction pathways of lymphocyte activation and proliferation. Subsequent studies demonstrated that the generation of soluble mediators such as nitric oxide by these adherent cells is responsible, albeit partially, for the down-regulation of the lymphoproliferative response in hamsters with visceral leishmaniasis. Received: 8 December 1998 / Accepted: 15 January 1999