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

PINO MARTÍNEZ AM; CRISTIAN GM; ESTELA I. BATALLA

Congreso; Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases; 2016

POSTER NUMBER: 1018IL10 plays an immunostimulatory role on CD8+ T cells during experimental Chagas diseaseAgustina Pino-Martinez, Cristian G. Miranda, Estela Batalla, Silvia Repetto, Stella M. Gonzalez-Cappa, Catalina DAlba SotoFacultad de Medicina, (IMPAM), UBA-CONICET, Universidad de Buenos. Argentina.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 thediverse immunoregulatory mechanisms elicited during experimentalT. cruzi infection which contribute to parasitepersistence 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 notconfer increased resistance to T. cruzi. In contrast, IL10KO infected mice exhibited higher parasitemia and parasiteload in tissues, weight loss and morbidity than their wild type counterparts. Next, we addressed the frequency of Tcells during acute infection (21d.p.i.). We found that IL10KO mice failed to expand the pool of splenic or circulatingCD8+ T cells, a feature of acute infection, without affecting the CD4+ T cells. Effector function of CD8+ T cells wasalso hampered in IL10KO infected mice. CD8+ T cells exhibited lower cytotoxic potential (CD107a), IFN-γproduction, lower survival and increased PD-1 expression than their WT counterparts. In the absence of IL10, CD8+ Tcells failed to reach critical infected organs (e.g. heart). At the chronic infection (5m.p.i.), infiltrates decreasedglobally 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 thatcontrols the intracellular stage of T. cruzi. In fact, expansion, activation and contraction of CD8+ T cells have greatimplications on the establishment of their memory potential. The fine understanding of mechanisms regulatingeffector function of this T cell population is critical for the rational design of effective vaccine strategies againstT.cruzi. Funded by ANPCYT, CONICET and F. Roemmers.