RESTORATION OF IFN-GAMMA PRODUCTION AND LYMPHOCYTE-PROLIFERATION IN VISCERAL LEISHMANIASIS

Visceral leishmaniasis is associated with a marked depression of T cel l responses, which has been characterized by the absence of IL-2 and I FN-gamma production by lymphocytes on in vitro stimulation with Leishm ania Ag. The aim of this study was to evaluate both the mechanism of t hese immunologic abnormalities and the restoration of in vitro T cell responses to Leishmania Ags. A total of 15 untreated visceral leishman iasis patients were evaluated. Although IFN-gamma and IL-4 levels in t he supernatants of lymphocyte cultures were very low or absent, mRNA f or these cytokines and for IL-10 were observed in PBMCs. Addition of I FN-gamma plus IL-2 enhanced lymphocyte proliferation by 158%. Restorat ion of T cell proliferative responses and lFN-gamma production was als o observed by the addition of a neutralizing mAb alpha-IL-10. Neutrali zing mAb alpha-IL-4 did not restore T cell responses but alpha-IL-10 a nd alpha-IL-4 mAbs had a synergistic effect on lymphocyte proliferatio n. The lFN-gamma levels in supernatants of lymphocyte cultures stimula ted with Leishmania chagasi Ag or L. chagasi Ag plus alpha-IL-4, alpha -IL-10, or alpha-IL-4 plus alpha-IL-10 mAbs were 26 +/- 30 pg/ml, 41 /- 18 pg/ml, 146 +/- 73 pg/ml, and 174 +/- 106 pg/ml, respectively. Th ese data indicate that Th2 cell activation occurs in visceral leishman iasis and that in vitro production of lFN-gamma and lymphocyte prolife ration can be restored by blocking the inhibitory effect of the Th2 cy tokines on mononuclear cells.