Leishmania major‐specific CD8+ T cells are inducers and targets of nitric oxide produced by parasitized macrophages

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Abstract
Lines of Leishmania major‐specific CD8+ T cells were derived from the lymph nodes and spleens of CBA mice, immune following resolution of a primary infection, 7 days after secondary challenge with viable L. major. Specific stimulation of these CD8+ T cells by bone marrow‐derived macrophages infected with L. major led to the release of interferon‐γ by CD8+ T cells and nitric oxide by macrophages. Interestingly, the nitric oxide released by bone marrow‐derived macrophages down‐regulated the production of interferon‐γ by specifically activated CD8+ T cells. The proliferation and long‐term maintenance of these parasite‐specific CD8+ T cells was impaired by the nitric oxide produced by stimulating infected macrophages as a result of cytokines released by activated CD8+ T cells. Taken together, the results indicate that L. major‐specific CD8+ T cells are sensitive to the toxic effect of the nitric oxide that they induce.