Early Treg cell depletion during Trypanosoma cruzi infection promotes Tconv and CD8+ T cell immunity in the acute phase

CL ARAUJO FURLAN; S BOCCARDO; C RODRIGUEZ; CL MONTES; A GRUPPI; EV ACOSTA RODRÍGUEZ

Congreso; Reunión de Sociedades de Biociencias 2021; 2021

SAIC - SAI - AAFE - NANOMED-AR

We reported that after Trypanosoma cruzi (Tc) infection, Tregs undergo a marked and sustained reduction in frequency. This natural contraction of the Treg response was critical to allow the emergence of protective anti-parasite CD8+T cell immunity in the acute phase. In line with this, we previously demonstrated that Treg depletion at day (d) 5 post-infection (pi) but not at d11pi impacted on the magnitude of anti-parasite CD8+T cell response and the ability to control parasite replication in the acute phase. Thus, we hypothesized that Tregs may exert a role during early events of T cell priming. In order to assess this, DEREG mice were infected with Tc and injected with diphtheria toxin (DT) or PBS at d5 and 6pi. However, DT treatment only induced modest effects on APCs shortly after the injection. Specially, CD86 expression was upregulated on splenic DCs, macrophages and NKT cells of DT-injected mice in contrast to controls (p<0.05), but no differences were observed in the expression of a range of innate immunity activation markers. In turn, we observed a significant increase in the numbers of Tconv cells of blood and liver at d11pi in DT-treated animals compared to control mice (p<0.05). This boost on Tconv cells in Treg-depleted animals was previous to the expansion of anti-parasite CD8+T cells observed at d20pi, suggesting a correlation between these two populations. Furthermore, Tconv cells from d11pi of DT-treated mice display an activated/effector phenotype, shown by the upregulation of CD44, PD-1 and CD25. At this time point after Treg cell depletion, CD8+T cells upregulate markers of early activation, however they show no changes in the expression of the proliferation marker Ki-67 nor in effector cell differentiation markers such us BATF, IRF4 and T-bet. Altogether, our results suggest that during Tc infection Tregs suppress CD8+T cell immunity at the acute phase through indirect mechanisms that involve the previous modulation of the Tconv cell response.