T cell response in murine Leishmania mexicana amazonensis infection: production of interferon-gamma by CD8+ cells

Abstract

The immune response to Leishmania major has been the subject of many investigations. However, Leishmania includes many species with different clinical manifestations. In this report, we studied the T cell response 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 important lymphokines that mediate macrophage activation and thus the destruction of the intracellular parasites, which lymphocyte subsets are producing the IFN-gamma is still a controversy. Much evidence including the isolation of protective, IFN-gamma-producing, CD4+ cell lines have confirmed the participation of CD4+ Th1 cells unequivocally. However, both CD4+ and CD8+ cells produced IFN-gamma. Recently, an increasing 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 C57BL/6 mice were eliminated by anti-CD8 antibody and complement-mediated lysis, the IFN-gamma production was reduced by 77%. This indicated that CD8+ cells produced a significant amount of the IFN-gamma. However, our results also indicate that IFN-gamma production by CD8+ cells was dependent on CD4+ cells.