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

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.