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

Stäger, Simona; Rafati, Sima

After activation, antigen-specific CD8 + T cells differentiate into effector cells and acquire the capacity to kill target cells, and produce several cytokines and chemokines (Kaech et al., 2002; Harty and Badovinac, 2008) . Among the various CD8 + T cell subsets, Tc1 were shown to play a major role in the fight against several protozoan parasites (Jordan and Hunter, 2010) . The hallmark of this subset is the production of IFN-γ and TNF, and cytotoxic capacity (Woodland and Dutton, 2003) . The precise mechanism underlying cytotoxic T lymphocyte (CTL) killing of microbes is still poorly understood. CTLs can exert cytotoxicity through various mechanisms: via exocytosis of lytic granula containing perforin, granzyme A/B, and/or granulysin; through the interaction between FasL and Fas expressed on targets cells; via TNF; or via TRAIL (Trapani and Smyth, 2002) . A study has also shown that reactivated memory CD8 + T cells efficiently killed Listeria monocytogenes via a mechanism mediated by CCL3 and involving the induction of radical oxygen intermediates (Narni-Mancinelli et al., 2007) . Direct killing of extracellular pathogen by CTLs has also been described. For example, CTLs can mediate killing of Mycobacterium tuberculosis through the release of anti-bacterial products (Stenger et al., 1998; Canaday et al., 2001) . However, direct killing of Schistosoma mansoni (Ellner et al., 1982) and Entamoeba histolytica (Salata et al., 1987) is thought to be contact-dependent. CTLs have also been reported to directly kill extracellular Toxoplasma gondii (Khan et al., 1990) . Interestingly, killing in this case appeared to be antigen-specific. To date there is no evidence that CD8 + T cells can mediate protection against Leishmania parasites through their cytotoxic activity. However, since CTLs have been www.frontiersin.org observed in various mouse models and also in human patients, a possible protective role for Leishmania-specific cytotoxic T cells should not be excluded.