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

CONSTANZA INSFRAN; AMBROSIO LAURA FERNANDA; HORACIO M SERRA; MOTRAN CRISTINA; VOLPINI XIMENA

BUENOS AIRES

Congreso; REUNION CONJUNTA DE SOCIEDADES DE BIOCEINCIAS; 2017

The generation and persistence of memory T cells that can provide long-lasting protection against pathogens is depending on signals given by dendritic cells (DC) during the antigen presentation. Thus, changes in any of the factors controlling the activation of T cells during antigen presentation by DC can regulate T effector and memory cell differentiation. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that controls several aspects of immune responses, including the modulation of DC activation and the differentiation of specific T cell subsets. Using B6 WT and B6 mice carrying a mutant AhR protein with reduced affinity for its ligands (AhRd) we demonstrated that AhR activation by endogenous ligands generated during T. cruzi infection restricts the differentiation of CD8+ memory T cells. To continue with these studies, we tested the hypothesis that the activation of AhR by weak ligands might contribute to restrict CD8+ memory T cell induction. For that T. cruzi infected B6 mice were treated with vehicle or 3-HK (an AhR weak ligand that is generated during the infection) from day 5 to 10 post infection (pi) plus ITE (a weak AhR ligand used in different clinical trials) on days 7, 9 and 11 pi, and the effector phase of memory induction was studied by FACS at day 13 and 21 pi. The treatment of T. cruzi-infected B6 mice with 3-HK+ITE induced a significant increase in the percentage of CD8+ T cells specific for the inmunodominant epitope TSKB20 (ANYKFTLV) that showed short lived effector cells phenotype (SLECs: CD127lo KLRG1hi) (day 13, p