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

Stäger, Simona; Rafati, Sima

In the human disease, there is evidence that mixed T helper cytokine profiles are present, while healing and protection against reinfection are associated with dominant Th1 and CD8 + T cells. These findings suggest that it is the cytokine balance that activates or suppresses activation of macrophages harboring Leishmania parasites. This, in turn, determines the outcome of the infection. Thus treatments or antigen/adjuvant formulations that can alter the type of T helper response may change the course of disease (Da-Cruz et al., 2002; Rogers and Titus, 2004; Mohajery, 2007) . For this purpose, different vaccination strategies have been examined in animal models including leishmanization (Modabber, 1990) , killed parasite (Grimaldi, 1995) , live attenuated parasite (Titus et al., 1995) , and subsequently, subunit vaccines composed of recombinant or native proteins from different stages of the parasite's life cycle, and DNA vaccines (Skeiky et al., 1998; Webb et al., 1998; Stager et al., 2000; Bottrel et al., 2001; Campos-Neto et al., 2001; Rafati et al., 2001; Coler et al., 2002) . The latter two strategies encompass candidates such as gp63, gp46, LACK, CPB, CPA, Kmp11, LmsTI1, TSA, LeIF, HASPB1, and LPG, and have shown promising results in murine models. Nonetheless, only Leish111f (a recombinant fusion protein of LmsTI1, TSA, and LeIF) progressed through phase I and II clinical trials (Llanos-Cuentas et al., 2010; Chakravarty et al., 2011) .