J Exp Med. 2014 Mar 31. [Epub ahead of print]

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

Cortez VS¹, Cervantes-Barragan L, Song C, Gilfillan S, McDonald KG, Tussiwand R, Edelson BT, Murakami Y, Murphy KM, Newberry RD, Sibley LD, Colonna M.

 

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.

PMID:

24687959

[PubMed - as supplied by publisher]