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

INSFRÁN CONSTANZA; AMBROSIO LAURA FERNANDA; VOLPINI XIMENA; SERRA HORACIO MARCELO; MOTRAN CLAUDIA CRISTINA

Buenos Aires

Congreso; LXIII Reunion Anual de la Sociedad Argentina de Inmunología; 2015

Sociedad Argentina de Inmunología

Abstract: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays important roles in several biological processes as development, detoxification and the immune response. Although the cellular immune response to virus infections is sensitive to modulation by AhR agonists, very little is known regarding how AhR activation affects T cell response during parasite infections. We have reported that T.cruzi infection up-regulates the expression of AhR in splenic cells with the TCDD-induced AhR activation impairing the host resistance to infection. To investigate the role of TCDD-induced AhR activation 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+ T cells and CD8+ T cells specific for the inmunodominant epitope TSKB20 (ANYKFTLV) at day 10 pi. Analysis of CD62L versus CD44 expression in CD8+ cells showed that TCDD-treatment significantly decreased the frequency of CD44hi CD62Llow cells (effector memory cells, EM) at expenses of CD44hi CD62Lhi cells (central memory cells, CM). Interestingly, the frequency of TSKB20-specific CD8+ T cells in CD8+ CM or EM gated subpopulations showed a significant decrease in TI compared with CI mice, suggesting a direct effect of TCDD on antigen-experienced CD8+ T cells. These findings reveal a key role for strong AhR activation in the control of mature memory CD8+ T cells and have major implications for the design of therapeutic and vaccination strategies.