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CD4+T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by G alpha(i)-coupled receptors but is CCR6-and CXCR3-independent

Svensson Frej, Marcus LU ; Russell, Karen; Mack, Matthias and Else, Kathryn J. (2010) In Immunology 129(2). p.257-267
Abstract
P>Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4+ T cells play a critical role in protective immunity, and that CD4+ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4+ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4+ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in... (More)
P>Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4+ T cells play a critical role in protective immunity, and that CD4+ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4+ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4+ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post-T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4+ T cells marked by down-regulation of CD62L. These cells can be isolated from intestine-draining mesenteric lymph nodes (MLN) from day 14 post-infection, but are rare or absent in MLN before this and in spleen at all times post-infection. Among CD4+ CD62Llow MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4+ CD62Llow T-cell migration to the large intestinal mucosa is dependent on the family of G alpha(i)-coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4+ CD62Llow cell migration to the large intestinal mucosa during T. muris infection. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
helminths, mucosal immunity, trafficking, receptors, chemokine, Th17), Th3, Th2, Th1, Th0, CD4, helper T cells (Th cells
in
Immunology
volume
129
issue
2
pages
257 - 267
publisher
Wiley-Blackwell
external identifiers
  • wos:000273458000011
  • scopus:73949129043
ISSN
0019-2805
DOI
10.1111/j.1365-2567.2009.03178.x
language
English
LU publication?
yes
id
0beea8f3-3d86-4b58-a4c3-6acb0e1b4b39 (old id 1547841)
date added to LUP
2010-02-23 08:35:22
date last changed
2018-05-29 10:01:28
@article{0beea8f3-3d86-4b58-a4c3-6acb0e1b4b39,
  abstract     = {P>Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4+ T cells play a critical role in protective immunity, and that CD4+ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4+ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4+ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post-T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4+ T cells marked by down-regulation of CD62L. These cells can be isolated from intestine-draining mesenteric lymph nodes (MLN) from day 14 post-infection, but are rare or absent in MLN before this and in spleen at all times post-infection. Among CD4+ CD62Llow MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4+ CD62Llow T-cell migration to the large intestinal mucosa is dependent on the family of G alpha(i)-coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4+ CD62Llow cell migration to the large intestinal mucosa during T. muris infection.},
  author       = {Svensson Frej, Marcus and Russell, Karen and Mack, Matthias and Else, Kathryn J.},
  issn         = {0019-2805},
  keyword      = {helminths,mucosal immunity,trafficking,receptors,chemokine,Th17),Th3,Th2,Th1,Th0,CD4,helper T cells (Th cells},
  language     = {eng},
  number       = {2},
  pages        = {257--267},
  publisher    = {Wiley-Blackwell},
  series       = {Immunology},
  title        = {CD4+T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by G alpha(i)-coupled receptors but is CCR6-and CXCR3-independent},
  url          = {http://dx.doi.org/10.1111/j.1365-2567.2009.03178.x},
  volume       = {129},
  year         = {2010},
}