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

ARAUJO FURLAN C.; TOSELLO BOARI J.; RODRIGUEZ C.; CANALE F.; FIOCCA VERNENGO F.; BECCARIA, C.; GRUPPI A.; MONTES C.; ACOSTA RODRIGUEZ E.

Buenos Aires

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015

Sociedad Argentina de Inmunología

CD4+CD25+Foxp3+ regulatory T cells (Tregs) present a dual role during infections as they limit immunopathology but also restrain immunity to the pathogen. Regulatory responses during T. cruzi (Tc) infection have been poorly characterized and Tregs role remains controversial. We previously determined that after 11 days (d) of infection, Tregs frequency is significantly reduced in the periphery of infected mice, in part due to impaired induction of peripheral Tregs.Here, our aim was to better characterize Tregs phenotype and function and their biological relevance during Tc infection. For this, Foxp3-GFP mice were infected with 5000 Tc (Tulahuén) and Tregs were characterized by flow cytometry. Upon infection, Tregs upregulated CD44, CTLA-4, GITR, PD1, CD39, CXCR3 and CD103 expression, consistent with activated phenotype. Furthermore, at d20 post-infection (pi) a large proportion of Tregs produced LAP and IL-10. However, in vitro suppression assays using Tregs purified from non-infected or 20-day-infected mice revealed that Tregs suppressive capacity is not increased by activation mediated by Tc. To assess the role of reduced Tregs frequency in Tc infection, we performed adoptive transfer experiments of in vitro induced Tregs. Intravenous injection of Tregs at d11pi resulted in a significant decrease in the frequency and numbers of total and parasite-specific CD8+ T cells in the spleen and liver at d17pi. Accordingly, these mice showed increased parasitemia. We conclude that the limitation in the numbers of activated Tregs during Tc infection may be critical to allow the development of the effector response and parasite control, but might also foster immunopathology.