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

Stäger, Simona; Rafati, Sima

Despite the documented evidence that CD8 + T cells strongly participate in the immune response to L. donovani and L. infantum, our recent findings suggest that L. donovani induces defective antigen-specific CD8 + T cell responses (Joshi et al., 2009 ). Interestingly, mice infected with L. donovani generate CD8 + T cell responses with limited clonal expansion. The extension of the clonal expansion is thought to be correlated with the effectiveness in eliminating pathogens. It was calculated that a naïve CD8 + T cell may go through 19 cell divisions in the first week after pathogen inoculation (Badovinac et al., 2007) . Massive clonal expansions have not only been observed during viral infections, but also following the injection of irradiated Plasmodium berghei sporozoites (Sano et al., 2001) . During L. donovani infection, CD8 + T cells underwent at least 8-9 rounds of division, but failed to accumulate in the spleen (Joshi et al., 2009) . Moreover, only 10% of CD8 + T cells during clonal expansion expressed markers typically associated with end-differentiated effector cells, such as KLRG1, unpublished) . The cause of this limited expansion is yet unknown and may depend on several factors. One of the possible explanations is limited antigen availability that may result from poor antigen-processing and presentation. Processing of Leishmania antigens is thought to be confined to a TAP-independent, intraphagosomal pathway that is less efficient and requires higher amounts of antigen than the endoplasmic reticulum-based, TAP-dependent cross-presentation pathway (Bertholet et al., 2006) . Furthermore, the major surface protease of Leishmania, gp63, was shown to cleave epitopes within the parasitophorous vacuole, further reducing antigen availability (Garcia et al., 1997) . Hence, Leishmania antigens may be poorly presented and this poor presentation may not be enough to induce and sustain a massive clonal expansion of antigen-specific CD8 + T cells.