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Selective Generation of Gut Tropic T Cells in Gut-associated Lymphoid Tissue (GALT): Requirement for GALT Dendritic Cells and Adjuvant.

Johansson Lindbom, Bengt LU ; Svensson Frej, Marcus LU ; Wurbel, Marc-Andre; Malissen, Bernard; Marquez, Gabriel and Agace, William LU (2003) In Journal of Experimental Medicine 198(6). p.963-969
Abstract
n the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin {alpha}4ß7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model,... (More)
n the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin {alpha}4ß7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+{alpha}4ß7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lymphocytes, antigen-presenting cell, inflammation, chemokines, intestinal mucosa
in
Journal of Experimental Medicine
volume
198
issue
6
pages
963 - 969
publisher
Rockefeller University Press
external identifiers
  • wos:000185416200013
  • pmid:12963696
  • scopus:0141449950
ISSN
1540-9538
DOI
10.1084/jem.20031244
language
English
LU publication?
yes
id
44c0ee98-387b-4b99-be4f-2bd37f3ff837 (old id 117884)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12963696&dopt=Abstract
date added to LUP
2007-07-16 09:32:35
date last changed
2018-09-23 04:11:31
@article{44c0ee98-387b-4b99-be4f-2bd37f3ff837,
  abstract     = {n the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin {alpha}4ß7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+{alpha}4ß7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.},
  author       = {Johansson Lindbom, Bengt and Svensson Frej, Marcus and Wurbel, Marc-Andre and Malissen, Bernard and Marquez, Gabriel and Agace, William},
  issn         = {1540-9538},
  keyword      = {lymphocytes,antigen-presenting cell,inflammation,chemokines,intestinal mucosa},
  language     = {eng},
  number       = {6},
  pages        = {963--969},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Selective Generation of Gut Tropic T Cells in Gut-associated Lymphoid Tissue (GALT): Requirement for GALT Dendritic Cells and Adjuvant.},
  url          = {http://dx.doi.org/10.1084/jem.20031244},
  volume       = {198},
  year         = {2003},
}