Reduced frequency of activated Foxp3+ regulatory T cells allows the emergence of specific CD8+ T cell immunity during T. cruzi infection.

ACOSTA RODRÍGUEZ, EVA; BOCCARDO, SANTIAGO; RODRÍGUEZ CONSTANZA; GRUPPI, ADRIANA; CANALE, FERNANDO P.; ARAUJO FURLAN CINTIA LILIANA; MONTES, CAROLINA L.; FIOCCA VERNENGO, FACUNDO; TOSELLO BOARI, JIMENA

Buenos Aires

Congreso; LXV Reunión Anual de la Sociedad Argentina de Inmunología; 2017

Sociedad Argentina de Inmunología

CD4+ Foxp3+ T cells (Tregs) present a dual role in infections asthey limit immunopathology but also restrain immunity to the pathogen.During T. cruzi (Tc) infection Tregs response has been poorlycharacterized. We previously determined that during this infection,Tregs become activated, upregulate a wide range of suppressivemarkers and acquire a transcriptional program specialized in controllingTh1 responses. However, Tregs frequency is significantlyreduced in the periphery of infected mice as a result of a low proliferationrate and impaired induction of peripheral Tregs.Here, our aim was to assess the biological relevance of reducedTregs frequency in Tc infection. First, we adoptively transferredTregs generated in vitro from naïve CD4 T cells cultured with IL-2, TFG-b and all-trans retinoic acid. Injection was performed atday (d) 11 post-infection (pi) in WT mice. At d17pi, Tregs recipientmice showed increased parasite burden in blood, spleen and liverconcomitantly with decreased frequency and numbers of totaland Tc-specific CD8 T cells compared to non-transferred animals.No differences were observed between the two groups in the levelsof biochemical damage markers. As a second approach, Tregswere specifically depleted by the injection of diphtheria toxin (DT)in DEREG mice at d5pi. Significantly reduced Tc levels and augmentedparasite specific CD8 response were observed in spleenand liver of DT-treated DEREG mice in comparison to PBS-injectedcounterparts at d19pi. CD8 functionality was also improved by Tregsdepletion, as shown by the significant increase in the frequency ofsplenic specific CD8 cells able to degranulate (CD107a+) and produceIFN-g and TNF upon parasite-specific stimulation in DT-treatedDEREG mice. These results outstand Tregs role during acute Tcinfection, suggesting that a reduction in activated Tregs frequencymay be necessary to allow the development of the CD8 T cell immunityresponsible of parasite control.