Differential homing mechanisms regulate regionalized effector CD8 alpha beta(+) T cell accumulation within the small intestine
Author
Summary, in English
The CC chemokine receptor (CCR)9 is expressed on the majority of small intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been proposed to play a central role in regulating small intestinal but not colonic immune responses and thus to organize regionalized immunity within the intestinal mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by epithelial cells in the distal compared with proximal small intestine, which correlated with less efficient CCR9-dependent effector CD8 alpha ss(+) T cell entry into the ileal epithelium. In vitro-generated alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry into the lamina propria was less dependent on CCR9 than entry into the epithelium along the entire length of the small intestine and in particular in the ileum. CCR9-independent alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry was pertussis toxin-sensitive, suggesting a role for additional Gal-linked G protein-coupled receptors. Finally, in vivo-primed effector CD8 alpha ss(+) T cells displayed regionalized differences in their entry to the small intestinal epithelium with enhanced CCR9-independent entry to the ileum. These results highlight a hitherto underappreciated compartmentalization of immune responses within the small intestine and have direct implications for targeting strategies aimed at regulating T cell localization to the small intestinal mucosa.
Department/s
- Immunology
Publishing year
2007
Language
English
Pages
10122-10127
Publication/Series
Proceedings of the National Academy of Sciences
Volume
104
Issue
24
Document type
Journal article
Publisher
National Academy of Sciences
Topic
- Immunology in the medical area
Keywords
- chemokine receptor
- intestinal mucosa
Status
Published
Research group
- Immunology
ISBN/ISSN/Other
- ISSN: 1091-6490