CONICET | Buscador de Institutos y Recursos Humanos

We have previously demonstrated that after Trypanosoma cruzi (Tc) infection, Tregs undergo a marked reduction in frequency that was sustained over time. This natural contraction of the activated Treg response appeared 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 Tregs in 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 days later, the effect of Tregs depletion was evaluated. Different from our previous results obtained in the acute phase, where DT-treated DEREG mice showed increased Tc-specific CD8+T cells numbers (p≤0.0426) in spleen and liver at d19pi, mice treated under the depletion scheme in the chronic phase showed similar numbers of total and parasite-specific CD8+T cells in spleen and Tc-target tissues. When CD4+T cells were evaluated, their frequency showed a small but significant increase in the spleen of Tregs-depleted mice compared to the control group (p=0.0116). This increase affected particularly a subset of CD4+T cells that showed the ability to degranulate (CD107a+, alone or in combination with TNF production) and may play pathogenic roles during chronic infections. Our results suggest that Tregs might play a deleterious role during the acute phase of Tc infection by suppressing protective CD8+T cells, while they would be beneficial during chronicity by regulating potentially pathogenic cytotoxic CD4+T cells.