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: Victor S Cortez, Luisa Cervantes-Barragan, Christina Song, Susan Gilfillan, Keely G McDonald, Roxane Tussiwand, Brian T Edelson, Yoshinori Murakami, Kenneth M Murphy, Rodney D Newberry, L David Sibley, Marco Colonna
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 211 Issue 4 Pg. 623-33 (Apr 07 2014) ISSN: 1540-9538 [Electronic] United States
• PMID: 24687959 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cadm1 protein, mouse
• Cell Adhesion Molecule-1
• Cell Adhesion Molecules
• Cytokines
• Immunoglobulins
• Interleukin-17
• Ligands
• class-I restricted T cell-associated molecule

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Adhesion Molecule-1
• Cell Adhesion Molecules (metabolism)
• Cell Polarity
• Cytokines (biosynthesis)
• Dendritic Cells (metabolism)
• Gastrointestinal Tract (immunology, parasitology, pathology)
• Immunoglobulins (deficiency, metabolism)
• Interleukin-17 (metabolism)
• Intestinal Mucosa (immunology, parasitology, pathology)
• Ligands
• Lymphocyte Count
• Mice
• Mice, Inbred C57BL
• Neutralization Tests
• Th17 Cells (immunology)
• Toxoplasma (physiology)
• Toxoplasmosis, Animal (immunology, parasitology)