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Gut associated lymphoid tissue primed CD4+ T cells display CCR9 dependent and independent homing to the small intestine.

Stenstad, Hanna LU ; Ericsson, Anna LU ; Johansson Lindbom, Bengt LU ; Svensson Frej, Marcus LU ; Marsal, Jan LU ; Mack, Matthias; Picarella, Dominic; Soler, Dulce; Marquez, Gabriel and Briskin, Mike, et al. (2006) In Blood 107(9). p.3447-3454
Abstract
CD4(+) T-cell entry to the intestinal mucosa is central to the generation of mucosal immunity as well as chronic intestinal inflammation, yet the mechanisms regulating this process remain poorly defined. Here we show that murine small intestinal CD4+ lamina propria lymphocytes express a heterogeneous but restricted array of chemokine receptors including CCR5, CCR6, CCR9, CXCR3, and CXCR6. CD4+ T-cell receptor transgenic OT-II cells activated in mesenteric lymph nodes acquired a distinct chemokine receptor profile, including expression of CCR6, CCR9, and CXCR3 that was only partially reproduced in vitro after priming with mesenteric lymph node dendritic cells. A subset of these effector CD4(+) T cells, expressing CD69 and alpha(4)beta(7),... (More)
CD4(+) T-cell entry to the intestinal mucosa is central to the generation of mucosal immunity as well as chronic intestinal inflammation, yet the mechanisms regulating this process remain poorly defined. Here we show that murine small intestinal CD4+ lamina propria lymphocytes express a heterogeneous but restricted array of chemokine receptors including CCR5, CCR6, CCR9, CXCR3, and CXCR6. CD4+ T-cell receptor transgenic OT-II cells activated in mesenteric lymph nodes acquired a distinct chemokine receptor profile, including expression of CCR6, CCR9, and CXCR3 that was only partially reproduced in vitro after priming with mesenteric lymph node dendritic cells. A subset of these effector CD4(+) T cells, expressing CD69 and alpha(4)beta(7), entered the intestinal lamina propria and the majority of these cells expressed CCR9. CCR9(-/-) OT-II cells were disadvantaged in their ability to localize to the intestinal lamina propria; however, they were readily detected at this site and expressed 047, but little CCR2, CCR5, CCR6, CCR8, CCR10, CXCR3, or CXCR6. Thus, whereas CD4(+) T cells activated in gut-associated lymphoid tissue express a restricted chemokine receptor profile, including CCR9, targeting both CCR9-dependent and CCR9-independent entry mechanisms is likely to be important to maximally inhibit accumulation of these cells within the small intestinal mucosa. (Less)
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type
Contribution to journal
publication status
published
subject
in
Blood
volume
107
issue
9
pages
3447 - 3454
publisher
American Society of Hematology
external identifiers
  • wos:000237217600018
  • pmid:16391017
  • scopus:33646415627
ISSN
1528-0020
DOI
10.1182/blood-2005-07-2860
language
English
LU publication?
yes
id
767e5e82-8d18-4cda-8c17-a19f76303251 (old id 150554)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16391017&dopt=Abstract
date added to LUP
2007-07-30 16:00:29
date last changed
2019-04-10 01:53:35
@article{767e5e82-8d18-4cda-8c17-a19f76303251,
  abstract     = {CD4(+) T-cell entry to the intestinal mucosa is central to the generation of mucosal immunity as well as chronic intestinal inflammation, yet the mechanisms regulating this process remain poorly defined. Here we show that murine small intestinal CD4+ lamina propria lymphocytes express a heterogeneous but restricted array of chemokine receptors including CCR5, CCR6, CCR9, CXCR3, and CXCR6. CD4+ T-cell receptor transgenic OT-II cells activated in mesenteric lymph nodes acquired a distinct chemokine receptor profile, including expression of CCR6, CCR9, and CXCR3 that was only partially reproduced in vitro after priming with mesenteric lymph node dendritic cells. A subset of these effector CD4(+) T cells, expressing CD69 and alpha(4)beta(7), entered the intestinal lamina propria and the majority of these cells expressed CCR9. CCR9(-/-) OT-II cells were disadvantaged in their ability to localize to the intestinal lamina propria; however, they were readily detected at this site and expressed 047, but little CCR2, CCR5, CCR6, CCR8, CCR10, CXCR3, or CXCR6. Thus, whereas CD4(+) T cells activated in gut-associated lymphoid tissue express a restricted chemokine receptor profile, including CCR9, targeting both CCR9-dependent and CCR9-independent entry mechanisms is likely to be important to maximally inhibit accumulation of these cells within the small intestinal mucosa.},
  author       = {Stenstad, Hanna and Ericsson, Anna and Johansson Lindbom, Bengt and Svensson Frej, Marcus and Marsal, Jan and Mack, Matthias and Picarella, Dominic and Soler, Dulce and Marquez, Gabriel and Briskin, Mike and Agace, William},
  issn         = {1528-0020},
  language     = {eng},
  number       = {9},
  pages        = {3447--3454},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Gut associated lymphoid tissue primed CD4+ T cells display CCR9 dependent and independent homing to the small intestine.},
  url          = {http://dx.doi.org/10.1182/blood-2005-07-2860},
  volume       = {107},
  year         = {2006},
}