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CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa.

Svensson Frej, Marcus LU ; Marsal, Jan LU ; Ericsson, Anna; Carramolino, Laura; Brodén, Therese LU ; Márquez, Gabriel and Agace, William LU (2002) In Journal of Clinical Investigation 110(8). p.1113-1121
Abstract
The recruitment of antigen-specific T lymphocytes to the intestinal mucosa is central to the development of an effective mucosal immune response, yet the mechanism by which this process occurs remains to be fully defined. Here we show that the CC chemokine receptor 9 (CCR9) is selectively and functionally expressed on murine alpha(E)beta(7)(+) naive CD8alphabeta(+) lymphocytes and a subset of recently activated CD69(+) CD8alphabeta(+) lymphocytes. Using a T cell receptor transgenic transfer model, we demonstrate that CCR9 expression is functionally maintained on CD8alphabeta(+) lymphocytes following activation in mesenteric lymph nodes but rapidly downregulated on CD8alphabeta(+) lymphocytes activated in peripheral lymph nodes. These... (More)
The recruitment of antigen-specific T lymphocytes to the intestinal mucosa is central to the development of an effective mucosal immune response, yet the mechanism by which this process occurs remains to be fully defined. Here we show that the CC chemokine receptor 9 (CCR9) is selectively and functionally expressed on murine alpha(E)beta(7)(+) naive CD8alphabeta(+) lymphocytes and a subset of recently activated CD69(+) CD8alphabeta(+) lymphocytes. Using a T cell receptor transgenic transfer model, we demonstrate that CCR9 expression is functionally maintained on CD8alphabeta(+) lymphocytes following activation in mesenteric lymph nodes but rapidly downregulated on CD8alphabeta(+) lymphocytes activated in peripheral lymph nodes. These recently activated CCR9(+) CD8alphabeta(+) lymphocytes selectively localized to the small-intestinal mucosa, and in vivo neutralization of the CCR9 ligand, CCL25, reduced the ability of these cells to populate the small-intestinal epithelium. Together these results demonstrate an important role for chemokines in the localization of T lymphocytes to the small-intestinal mucosa and suggest that targeting CCL25 and/or CCR9 may provide a means to selectively modulate small-intestinal immune responses. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
110
issue
8
pages
1113 - 1121
publisher
The Journal of Clinical Investigation
external identifiers
  • pmid:12393847
  • wos:000178793700010
  • scopus:0036802422
ISSN
0021-9738
DOI
10.1172/JCI200215988
language
English
LU publication?
yes
id
8be51839-79c0-48e7-a14e-07d3e5520c5c (old id 110518)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12393847&dopt=Abstract
date added to LUP
2007-07-19 15:30:35
date last changed
2017-10-22 04:50:21
@article{8be51839-79c0-48e7-a14e-07d3e5520c5c,
  abstract     = {The recruitment of antigen-specific T lymphocytes to the intestinal mucosa is central to the development of an effective mucosal immune response, yet the mechanism by which this process occurs remains to be fully defined. Here we show that the CC chemokine receptor 9 (CCR9) is selectively and functionally expressed on murine alpha(E)beta(7)(+) naive CD8alphabeta(+) lymphocytes and a subset of recently activated CD69(+) CD8alphabeta(+) lymphocytes. Using a T cell receptor transgenic transfer model, we demonstrate that CCR9 expression is functionally maintained on CD8alphabeta(+) lymphocytes following activation in mesenteric lymph nodes but rapidly downregulated on CD8alphabeta(+) lymphocytes activated in peripheral lymph nodes. These recently activated CCR9(+) CD8alphabeta(+) lymphocytes selectively localized to the small-intestinal mucosa, and in vivo neutralization of the CCR9 ligand, CCL25, reduced the ability of these cells to populate the small-intestinal epithelium. Together these results demonstrate an important role for chemokines in the localization of T lymphocytes to the small-intestinal mucosa and suggest that targeting CCL25 and/or CCR9 may provide a means to selectively modulate small-intestinal immune responses.},
  author       = {Svensson Frej, Marcus and Marsal, Jan and Ericsson, Anna and Carramolino, Laura and Brodén, Therese and Márquez, Gabriel and Agace, William},
  issn         = {0021-9738},
  language     = {eng},
  number       = {8},
  pages        = {1113--1121},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa.},
  url          = {http://dx.doi.org/10.1172/JCI200215988},
  volume       = {110},
  year         = {2002},
}