CD8(+) T Cells in Leishmania Infections: Friends or Foes?

Stäger, Simona; Rafati, Sima

The role of CD8 + T cells in the immunity to L. major has always been controversial. Early studies in BALB/c mice reported that CD8 + T cells were the main mediators of protection following CD4 + T cell depletion in mice infected with L. major (Titus et al., 1987; Hill et al., 1989; Muller et al., 1991) . Interestingly, depletion of CD4 + T cells was rendering susceptible BALB/c mice resistant to L. major infection. The results obtained using the CD4 + T cell depletion model suggested that CD8 + T cells could potentially control L. major infection in mice. A few years later, experiments in β2-microgobulin-deficient mice contradicted these findings and revealed that CD8 + T cells were not essential in mediating protection in L. major-infected BALB/c mice (Wang et al., 1993) . Moreover, a study in CD8 + T cell-deficient mice demonstrated that Cd8 −/− mice were able to control L. major infection for at least 1 year, suggesting that CD8 + T cells were not required for long-lasting immunity (Huber et al., 1998) . The contribution of CD8 + T cells in the control of primary L. major infection became less important also because of the strong evidence that Th1 cells were the primary cells involved in mediating protection against cutaneous leishmaniasis (Reiner and Locksley, 1995; Louis et al., 1998; Sacks and Noben-Trauth, 2002) . Several studies have demonstrated that Th1 cells producing IFN-γ were essential in controlling L. major infection, and that failure to develop a Th1 response resulted in susceptibility to the diseases. Hence, a consensus was reached in that if a mouse generates Th2 responses, this will lead to susceptibility; in contrast, Th1 responses were successfully controlling infection without the help of CD8 + T cells.