Leishmania infantum‐specific T cell lines derived from asymptomatic dogs that lyse infected macrophages in a major histocompatibility complex‐restricted manner

Protective immunity to leishmaniasis has been demonstrated in murine models to be mediated by T cells and the cytokines they produce. We have previously shown that resistance to experimental Leishmania infantum infection in the dog, a natural host and reservoir of the parasite, is associated with the proliferation of peripheral blood mononuclear cells (PBMC) to parasite antigen and to the production of interleukin‐2 and tumour necrosis factor. In this study we show that PBMC from asymptomatic experimentally infected dogs produce interferon‐γ upon parasite antigen‐specific stimulation, whereas lymphocytes from symptomatic dogs do not. In addition, we report for the first time the lysis of L. infantum‐infected macrophages by PBMC from asymptomatic dogs and by parasite‐specific T cell lines derived from these animals. These T cell lines were generated by restimulation in vitro with parasite soluble antigen and irradiated autologous PBMC as antigen‐presenting cells. We show that lysis of infected macrophages by T cell lines is major histocompatibility complex restricted. Characterization of parasite‐specific cytotoxic T cell lines revealed that the responding cells are CD8⁺. However, for some animals, CD4⁺ T cells that lyse infected macrophages were also found. In contrast to asymptomatic dogs, lymphocytes from symptomatic dogs failed to proliferate and produce interferon‐γ after Leishmania antigen stimulation in vitro and were not capable of lysing infected macrophages. These results suggest that both the production of interferon‐γ and the destruction of the parasitized host cells by Leishmania‐specific T cells play an important role in resistance to visceral leishmaniasis.