WEAK AHR SIGNALING RESTRICTS THE DIFFERENTIATION OF CD8+ MEMORY T CELLS DURING TRYPANOSOMA CRUZI INFECTION

AMBROSIO, LF; CLAUDIA MOTRAN; VOLPINI, XIMENA; INSFRAN, CONSTANZA; SERRA, HORACIO

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC-SAI

The generation and persistence of memory T cells that can providelong-lasting protection against pathogens is depending on signalsgiven by dendritic cells (DC) during the antigen presentation.Thus, changes in any of the factors controlling the activation of Tcells during antigen presentation by DC can regulate T effector andmemory cell differentiation. The aryl hydrocarbon receptor (AhR) isa ligand-activated transcription factor that controls several aspectsof immune responses, including the modulation of DC activation andthe differentiation of specific T cell subsets. Using B6 WT and B6 ligands(AhRd) we demonstrated that AhR activation by endogenousligands generated during T. cruzi infection restricts the differentiationof CD8+ memory T cells. To continue with these studies, wetested the hypothesis that the activation of AhR by weak ligandsmight contribute to restrict CD8+ memory T cell induction. For thatT. cruzi infected B6 mice were treated with vehicle or 3-HK (an AhRweak ligand that is generated during the infection) from day 5 to10 post infection (pi) plus ITE (a weak AhR ligand used in differentclinical trials) on days 7, 9 and 11 pi, and the effector phase ofmemory induction was studied by FACS at day 13 and 21 pi. Thetreatment of T. cruzi-infected B6 mice with 3-HK+ITE induced a significantincrease in the percentage of CD8+ T cells specific for theinmunodominant epitope TSKB20 (ANYKFTLV) that showed shortlived effector cells phenotype (SLECs: CD127lo KLRG1hi) (day 13,p