In contrast to the cutaneous models, CD8 + T cells have always been thought to play a major role in experimental visceral leishmaniasis (VL). Over 20 years ago, Stern et al. (1988) demonstrated for the first time that CD8 + T cells significantly contribute to the formation of granulomas in the liver of L. donovani-infected mice. Indeed, CD8 + T cell depletion resulted in impaired granuloma formation and exacerbation of liver disease. In agreement with these results, Kaye et al. (1992) also reported a delayed onset and a decrease of the liver granulomatous response in non-obese, diabetic mice expressing transgenic I-E molecules, suggesting that antigen-specific CD8 + T cells are required for proper granuloma formation. CD8 + T cells appear to participate in controlling parasite growth in the spleen as well, since CD8 + T cell depletion during chronic VL significantly increased splenic parasite burden (Stäger, unpublished) . This observation was underscored by the fact that adoptive transfer of antigen-specific CD8 + T cells during Frontiers in Immunology | Microbial Immunology chronic L. donovani infection resulted in 90% reduction in the splenic parasite burden (Polley et al., 2006) . Moreover, therapeutic vaccination aimed at reactivating CD8 + T cells during chronic VL ensued in the control of parasite growth in the spleen (Joshi et al., 2009) .