IL10 plays an immunostimulatory role on CD8+ T cells during experimental Chagas disease.

PINO-MARTINEZ, AGUSTINA MARIA; MIRANDA, CRISTIAN GABRIEL; BATALLA, ESTELA I; REPETTO, SILVIA ANALIA; GONZALEZ CAPPA, STELLA MARIS; ALBA SOTO, CATALINA D.

Cape Town

Workshop; New Approaches to Vaccines for Human and Veterinary Tropical Diseases; 2016

Keystone Symposia on Molecular and Cellular Biology

The regulatory cytokine IL10 is produced by different cell types in response to infection with the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. Our previous works show that IL-10 is involved in the diverse immunoregulatory mechanisms elicited during experimental T. cruzi infection which contribute to parasite persistence but also put a brake on immunopathology. Here, we infected mice deficient in IL10 (IL10KO, Balb-c background) and found that absence of IL10 does not confer increased resistance to T. cruzi. In contrast, IL10KO infected mice exhibited higher parasitemia and parasite load in tissues, weight loss and morbidity than their wild type counterparts. Next, we addressed the frequency of T cells during acute infection (21d.p.i.). We found that IL10KO mice failed to expand the pool of splenic or circulating CD8+ T cells, a feature of acute infection, without affecting the CD4+ T cells. Effector function of CD8+ T cells was also hampered in IL10KO infected mice. CD8+ T cells exhibited lower cytotoxic potential (CD107a), IFN-γ production, lower survival and increased PD-1 expression than their WT counterparts. In the absence of IL10, CD8+ T cells failed to reach critical infected organs (e.g. heart). At the chronic infection (5m.p.i.), infiltrates decreased globally but IL10 still appeared necessary to direct CD8+ T cells to target tissues. In conclusion, IL10 plays a previously unrecognized immunostimulatory role on CD8+ T cells, the cell population that controls the intracellular stage of T. cruzi. In fact, expansion, activation and contraction of CD8+ T cells have great implications on the establishment of their memory potential. The fine understanding of mechanisms regulating effector function of this T cell population is critical for the rational design of effective vaccine strategies against T. cruzi.