title: 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.
authors.affiliation: Department of Pathology and Immunology, 2 Department of Internal Medicine, 3 Department of Molecular Microbiology, and 4 Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Cortez
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragan
authors.forename: Christina
authors.initials: C
authors.lastname: Song
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.forename: Keely G
authors.initials: KG
authors.lastname: McDonald
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016764:Cell Polarity; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D007136:Immunoglobulins / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008024:Ligands; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D058504:Th17 Cells / Q000276:immunology*; D014122:Toxoplasma / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007136:Immunoglobulins; D020381:Interleukin-17; D008024:Ligands; C408522:class-I restricted T cell-associated molecule