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-gamma 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-gamma 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 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.
Stefani
M M
MM
WHO Immunology Research, University of Lausanne, Epalinges, Switzerland.
Müller
I
I
Louis
J A
JA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases