Migration and retention of CD8 T cells within the intestinal epithelium (39.19)

Abstract

Abstract Memory CD8 T cells persist in the small intestinal epithelium in a highly activated state. To test whether an antigen reservoir or other enduring byproduct of infection was required for the maintenance of this phenotype, we transferred TCR transgenic CD8 T cells of fixed specificity into Rag deficient hosts. Firstly, introduction to a lymphopenic environment was sufficient to induce dissemination of donor T cells to the intestinal mucosa. Once there, they adopted the quintessential properties of small intestine lymphocytes including expression of CD69 and Granzyme B, suggesting that the maintenance of an activated phenotype within intestinal epithelium was independent of residual byproducts of infection. Notably, memory CD8 T cells within small intestinal epithelium express CD103 integrin, a ligand for epithelium expressed E-cadherin. Using virus specific TCR transgenic cells deficient for CD103, we assessed the role of this molecule in migration and maintenance. While cells deficient for CD103 migrated to intestinal epithelium without defect shortly after infection, they exhibited a profoundly reduced capacity to persist in that compartment after clearance of the infection. Thus, the establishment of a resident memory CD8 T population with an activated phenotype within the intestinal epithelium occurs in the absence of residual infectious byproducts and is largely dependent upon expression of CD103.