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

[摘要] 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.

[学科分类] 生理学

[关键词] CD8+ T cells;IL‐10;PD‐1;T cell activation;T cell exhaustion;Trypanosoma cruzi