IL-10 participates in the expansion and functional activation of CD8+ T cells during acute infection with Trypanosoma cruzi

Abstract

IL-10 is a pleiotropic cytokine with immunoregulatory functions affecting various cell types. In a model of experimental infection with the protozoan Trypanosoma cruzi (T. cruzi), we found increased morbidity and lower parasite control in IL-10 deficient mice (IL-10 KO) compared to wild-type (WT) mice. Despite enhanced Mϕ function and dendritic cell activation, IL-10 KO mice were more susceptible to infection. The kinetics of T cells in spleen and peripheral blood revealed that infected IL-10 KO mice failed to increase the number of spleen and circulating total CD8 + T cells, a phenomenon observed from the second week of infection in WT mice. Total CD8 + T cells from IL-10 KO mice exhibited diminished proliferation, cytotoxic potential and IFN-γ production than their WT counterparts and T. cruzi-specific CD8 + T cells displayed reduced in vivo cytotoxicity. The absence of IL-10 selectively affected expansion, survival, and increased PD-1 expression of CD8 + T cells without altering these same parameters on CD4 + T cells. Increased inhibitory receptors expression and down-modulation of T-bet by CD8 + T cells from IL-10 KO infected mice were compatible with a T cell exhaustion phenotype. Collectively, these findings reveal that during acute infection, IL-10 plays a previously unrecognized stimulatory role on CD8 + T cells, the most relevant lymphocyte population for the control of intracellular T. cruzi stages. A clear knowledge of the underlying mechanisms that drive effector functions of cytotoxic T cells is critical to understand pathogen persistence and rational design of prophylactic strategies against T. cruzi.