TH1 AND TH2 CELL-ASSOCIATED CYTOKINES IN EXPERIMENTAL VISCERAL LEISHMANIASIS

In experimental Leishmania donovani infection in BAtB/c mice, initial susceptibility gives way to T-cell-dependent acquired resistance and e ventual control over visceral infection. Since various cytokines appea r to underlie the host response to Leishmania infection, we examined i nfected liver tissue for gene expression of cytokines associated with Th1 (gamma interferon [IPN-gamma] and interleukin-2 [IL-2]) and Th2 ce lls (IL-4 and IL-10). By Northern (RNA) blot analysis, only IFN-gamma mRNA expression was detected in livers of infected euthymic mice, To d etermine whether activation of Th1 cells develops selectively in this model, qualitative PCR analysis nas used. These results indicated that mRNAs for IFN-gamma, IL-2, IL-4, and IL-10 were all induced by L. don ovani infection. The potentially negative Th2 cell-associated response did not appear to play a functional role, however, since resistance w as acquired, anti-IL-4 monoclonal antibody treatment did not accelerat e control over visceral infection, and serum immunoglobulin E levels r emained low. As judged by PCR analysis, IL-4 and IL-10 mRNAs were also expressed under three other conditions without apparent effect: in na ive euthymic mice treated with IL-2, which induces leishmanicidal acti vity; in rechallenged immune mice, which resist reinfection; and in nu de mice, which fail to control L. donovani. These results suggest that , like other Leishmania species, L. donovani infection may trigger a p otentially suppressive Th2 cell-associated cytokine response. However, in T-cell-intact mice able to control L. donovani, this response eith er is insufficient to influence outcome or more likely is overshadowed by the Th1 cell response,