T-CELL RESPONSE IN MURINE LEISHMANIA-MEXICANA-AMAZONENSIS INFECTION -PRODUCTION OF INTERFERON-GAMMA BY CD8+ CELLS

The immune response to Leishmania major has been the subject of many i nvestigations. However. Leishmania includes many species with differen t clinical manifestations. In this report, we studied the T cell respo nse to L. mexicana amazonensis, a New World species, in a murine model . We found that, similar to L. major, an Old World species, resistant C57BL/6 mice produced a high level of IFN-gamma and a low level of IL- 4. Conversely, susceptible BALB/c mice produced a much lower level of IFN-gamma and higher level of IL-4. Although IFN-gamma is one of the i mportant lymphokines that mediate macrophage activation and thus the d estruction of the intracellular parasites, which lymphocyte subsets ar e producing the IFN-gamma is still a controversy. Much evidence includ ing the isolation of protective, IFN-gamma-producing, CD4+ cell lines have confirmed the participation of CD4+ Th1 cells unequivocally. Howe ver, both CD4+ and CD8+ cells produced IFN-gamma. Recently, an increas ing body of evidence has appeared suggesting that CD8+ cells also play a role in the resolution of murine L. major infection. We found that in the L. m. amazonensis model, when CD8+ lymphocytes from resistant C 57BL/6 mice were eliminated by anti-CD8 antibody and complement-mediat ed lysis, the IFN-gamma production was reduced by 77%. This indicated that CD8+ cells produced a significant amount of the IFN-gamma. Howeve r, our results also indicate that IFN-gamma production by CD8+ cells w as dependent on CD4+ cells.