Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis

In contrast to euthymic (nu/+) BALB/c mice, athymic nude (nu/nu) BALB/c mice fail to control the visceral intracellular replication of Leishmania donovani, do not generate the macrophage-activating lymphokine IFN-gamma, and show little or no granulomatous tissue response. To characterize the T cell requirement for successful defense against L. donovani, nude mice were first reconstituted with unfractionated nu/+ immune spleen cells, which readily conferred the capacity to control and eliminate visceral (hepatic) L. donovani. In reconstituted mice, acquired resistance was paralleled by the ability of spleen cells to generate high levels of leishmanial Ag-stimulated IFN-gamma and the development of well formed liver granulomas. In contrast, nude mice reconstituted with either L3T4+- or Lyt-2+-enriched immune spleen cells alone failed to control visceral parasite replication and did not develop effective granulomas despite the finding that transfer of L3T4+ cells largely and Lyt-2+ cells partially restored the capacity to secrete IFN-gamma. To determine whether both T cell subsets were also required in a normal host, nu/+ BALB/c mice were treated with cell-depleting anti-L3T4 and anti-Lyt-2 mAb. Depletion of either T cell subset inhibited the acquisition of resistance to L. donovani and impaired the tissue granulomatous response. Thus, successful T cell-dependent host defense towards intracellular L. donovani and the tissue expression (granulomas) of this mechanism appear to require both L3T4+ and Lyt-2+ cells. A primary role for the L3T4+ cell may be IFN-gamma production; the role of the Lyt-2+ cell and the precise interaction of the two T cell subsets remain to be identified.