Additionally to the classical cytotoxic pathways, a novel counterregulatory function for a subset of cytotoxic CD8 + T cells has recently been proposed in the L. donovani infection model (Martin et al., 2010) . In this study, CD3 + CD8 + CD40 + T cells are shown to suppress regulatory T cells via CD40/CD40L interaction during the early stages of infection in BALB/c mice. CD40 signals through Ras, PI3K, and protein kinase C, leading to the induction of granzyme and perforin, and ultimately to the killing of Tregs.