Role of aryl hydrocarbon receptor (AhR) activation in the development of CD8+ T cell response during T. cruzi infection

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

CABA

Congreso; I meeting LASID SAI FAIC; 2015

LASID SAI

Abstract: Aryl hydrocarbon receptor (AhR) is a ligand-activatedtranscription factor that plays important roles in several biologicalprocesses as development, detoxification and the immuneresponse. Although the cellular immune response to virusinfections is sensitive to modulation by AhR agonists, very little isknown regarding how AhR activation affects T cell responseduring parasite infections. We have reported that T.cruzi infectionup-regulates the expression of AhR in splenic cells with theTCDD-induced AhR activation impairing the host resistance toinfection. To investigate the role of TCDD- induced AhRactivation in the development of parasite-specific CD8+ T cells,B6 mice were treated with 40 ug/kg of TCDD (TI) or vehicle (CI)one day prior to infection with 50000 T. cruzi trypomastigotes.This treatment severely impaired the frequency of blood CD8+ Tcells and CD8+ T cells specific for the inmunodominant epitopeTSKB20 (ANYKFTLV) at day 10 pi. Analysis of CD62L versusCD44 expression in CD8+ cells showed that TCDD-treatmentsignificantly decreased the frequency of CD44hi CD62Llow cells(effector memory cells, EM) at expenses of CD44hi CD62Lhicells (central memory cells, CM). Interestingly, the frequency ofTSKB20-specific CD8+ T cells in CD8+ CM or EM gatedsubpopulations showed a significant decrease in TI compared withCI mice, suggesting a direct effect of TCDD on antigenexperiencedCD8+ T cells. These findings reveal a key role forstrong AhR activation in the control of mature memory CD8+ Tcells and have major implications for the design of therapeutic andvaccination strategies