Inhibition of IL-2 induced IL-10 production as a principle of phase specific immuno-therapy for visceral leishmaniasis

Abstract

Visceral leishmaniasis is a fatal disease caused by the protozoan parasite Leishmania donovani. T cells are known to mediate resistance or susceptibility against this ‘neglected disease’ by the intricate cytokine milieu created by these cells during infection with L. donovani. Progression of visceral leishmaniasis is characterized by suppression of anti-leishmanial T cell responses, which was thought to be due to deficiency of interleukin-2, a potent T cell growth factor. The present study defies this to some extent, showing that during the first week of L. donovani infection, IL-2 induces IL-10 from antigen-primed T cells which suppresses the host-protective functions of infiltrating naïve T cells, in the later phase of infection. Host protection could be achieved by neutralizing IL-2/IL-2R and IL-10 at different time points after infection, which demonstrates their distinct roles at the priming and effector phases. This establishes a novel strategy of using kinetic modulation of an ongoing immune response as a principle of phase-specific immunotherapy for visceral leishmaniasis.