Distinct mucosal microenvironments differentially regulate memory T cell differentiation state and maintenance (39.20)

Abstract

Abstract T cell location and differentiation state are critical factors involved in protection against viral infection. We found that the phenotype of LCMV-specific CD8 and CD4 T cells varied by location, even amongst different mucosal tissues. Virus-specific CD8 T cells upregulated αE integrin and downregulated Ly6C in the small intestine but this did not occur in the spleen, lung, large intestine, or vaginal mucosa. αE integrin was required for maintenance of CD8 T cells in the small intestine IEL (see Casey et al. abstract). TGF β was responsible for inducing this tissue-specific phenotype. Interestingly, virus-specific CD4 T cells did not modify αE integrin and Ly6c in response to TGF β. Virus-specific CD4 T cells exhibited a decrease in αE integrin expression compared to CD8 T cells and this correlated with decreased maintenance of memory antigen-specific CD4 T cells within this compartment. Taken together, these data may explain why the abundant CD4 T cell effector response was poorly maintained specifically within the small intestine epithelium and highlights a mechanism by which tissue microenvironment regulates maintenance and compartmentalization of T cells in mucosal tissues.