CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection

Abstract

Retention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. We find that both CD4+CD8+ and CD4+ T cells in the intestinal epithelium, as well as CD8+ T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule class I-restricted T cell-associated molecule (Crtam) upon activation, whereas the ligand of Crtam, cell adhesion molecule 1 (Cadm1), is expressed on gut CD103+DCs. Lack of Crtam-Cadm1 interactions in Crtam-/- and Cadm1-/- mice results in loss of CD4+CD8+ T cells, which arise from mucosal CD4+ T cells that acquire a CD8 lineage expression profile. After acute oral infection with Toxoplasma gondii, both WT and Crtam-/- mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam-/- mice. The almost exclusive TH1 response in Crtam-/- mice resulted in more efficient control of intestinal T. gondii infection. Thus, Crtam-Cadm1 interactions have a major impact on the residency and maintenance of CD4+CD8+ T cells in the gut mucosa in the steady state. During pathogenic infection, Crtam-Cadm1 interactions regulate the dynamic equilibrium between newly formed CD4+ T cells and their retention in the gut, thereby shaping representation of disparate CD4+ T cell subsets and the overall quality of the CD4+ T cell response. © 2014 Cortez et al.