Role of food antigens on development and function of IELs (MUC8P.811)

Abstract

Abstract Intestinal IELs reside within the epithelial cell layer of the gut and are composed of several subsets of T cells, including induced TCRαβ+CD4+, TCRαβ+CD8αβ+, and TCRαβ+CD4+CD8αβ+ IELs, and natural TCRαβ+CD8αα+ and TCRγδ+CD8αα+ IELs. Their close proximity to the gut lumen and their intimate association with enterocytes presumably allow IELs to serve as the first line of defense against invading pathogens and to maintain homeostasis of the intestinal epithelial cells. Despite the fact that IELs have been studied for a long time, their exact biological function remains largely unknown. Early studies have revealed that intestinal colonization with commensal microbiota leads to expansion of TCRαβ+ IELs and their enhanced cytotoxic activity, indicating that a role for bacterial Ags in development and function of IELs. To investigate the role of food Ags in IELs, we analyzed IELs in offspring of germ-free B6 mice raised with elemental diet, designated as antigen-free mice. In antigen-free mice, we found a severe reduction in development of induced IELs, i.e., TCRαβ+CD4+, TCRαβ+CD8αβ+, and TCRαβ+CD4+CD8αβ+ IELs, and a partial depletion of natural TCRαβ+CD8αα+ IELs. The TCRγδ+CD8αα+ IEL population was relatively unaffected in antigen-free mice. We also observed a significant reduction in the ability of IELs to display effector function in antigen-free mice. Our results suggest that development and effector function of many subsets of IELs are strongly dependent on dietary antigens.