期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 211, 期 4, 页码 623-633出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20130904
关键词
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资金
- National Institutes of Health (NIH) [1U01AI095542, R01DE021255, R21CA16719]
- Infectious Disease Training Grant [T32 AI 7172-34]
- Swiss National Science Foundation [PBSKP3-134332]
- Swiss Foundation for Medical-Biological Grants [PASMP3-145751]
- NCI Cancer Center Support Grant [P30 CA91842]
- ICTS/CTSA Grant, a component of the NIH [UL1TR000448]
- NIH Roadmap for Medical Research
- Swiss National Science Foundation (SNF) [PASMP3_145751, PBSKP3_134332] Funding Source: Swiss National Science Foundation (SNF)
- Grants-in-Aid for Scientific Research [26640121] Funding Source: KAKEN
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.
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