Limited induction of Foxp3+ regulatory T cells during experimental Trypanosoma cruzi infection allows the generation of robust effector responses and parasite control

ARAUJO FURLLÁN C; TOSELLO BOARI J; RODRIGUEZ, C; CANALE F; FIOCCA F; BECCARÍA C; GRUPPI A; MONTES CL; ACOSTA RODRIGUEZ EV

Buenos Aires

Congreso; I meeting LASID, FAIC and SAI; 2015

LASID, FAIC, SAI

Abstract: CD4+CD25+Foxp3+ regulatory T cells (Tregs) present adual role during infections as they limit immunopathology but alsorestrain immunity to the pathogen. Regulatory responses during T.cruzi (Tc) infection have been poorly characterized and Tregs roleremains controversial. We previously determined that after 11days (d) of infection, Tregs frequency is significantly reduced inthe periphery of infected mice, in part due to impaired induction ofperipheral Tregs.Here, our aim was to better characterize Tregs phenotype andfunction and their biological relevance during Tc infection. Forthis, Foxp3-GFP mice were infected with 5000 Tc (Tulahuén) andTregs were characterized by flow cytometry. Upon infection,Tregs upregulated CD44, CTLA-4, GITR, PD1, CD39, CXCR3and CD103 expression, consistent with activated phenotype.Furthermore, at d20 post-infection (pi) a large proportion of Tregsproduced LAP and IL-10. However, in vitro suppression assaysusing Tregs purified from non-infected or 20-day-infected micerevealed that Tregs suppressive capacity is not increased byactivation mediated by Tc. To assess the role of reduced Tregsfrequency in Tc infection, we performed adoptive transferexperiments of in vitro induced Tregs. Intravenous injection ofTregs at d11pi resulted in a significant decrease in the frequencyand numbers of total and parasite-specific CD8+ T cells in thespleen and liver at d17pi. Accordingly, these mice showedincreased parasitemia. We conclude that the limitation in thenumbers of activated Tregs during Tc infection may be critical toallow the development of the effector response and parasitecontrol, but might also foster immunopathology.