Regulatory Foxp3+ T cells may suppress different cell populations and play divergent roles in acute versus chronic Trypanosoma cruzi infection.

BOCCARDO S; GRUPPI A; ACOSTA RODRIGUEZ EV; ARAUJO FURLÁN CL; MONTES CL

Congreso; LXVII Reunión Anual de la SAI.; 2019

We have previously demonstrated that after Trypanosoma cruzi (Tc) infection, Tregs undergo a markedreduction in frequency that was sustained over time. This natural contraction of the activated Treg responseappeared critical to allow the emergence of protective anti-parasite CD8+T cell immunity in the acute phase.In order to investigate the role of Tregs during Tc chronic infection, we performed specific depletion of Tregsin chronically infected animals. For this, DEREG mice were infected with 5000 trypomastigotes, and at days(d) 109 and 110 post-infection (pi) were injected with diphtheria toxin (DT) or PBS as control. Thirteen dayslater, the effect of Tregs depletion was evaluated. Different from our previous results obtained in the acutephase, where DT-treated DEREG mice showed increased Tc-specific CD8+T cells numbers (p≤0.0426) inspleen and liver at d19pi, mice treated under the depletion scheme in the chronic phase showed similarnumbers of total and parasite-specific CD8+T cells in spleen and Tc-target tissues. When CD4+T cells wereevaluated, their frequency showed a small but significant increase in the spleen of Tregs-depleted micecompared to the control group (p=0.0116). This increase affected particularly a subset of CD4+T cells thatshowed the ability to degranulate (CD107a+, alone or in combination with TNF production) and may playpathogenic roles during chronic infections. Our results suggest that Tregs might play a deleterious roleduring the acute phase of Tc infection by suppressing protective CD8+T cells, while they would be beneficialduring chronicity by regulating potentially pathogenic cytotoxic CD4+T cells.