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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Marcus Svensson Frej
  • Karen Russell
  • Matthias Mack
  • Kathryn J. Else
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • helminths, mucosal immunity, trafficking, receptors, chemokine, Th17), Th3, Th2, Th1, Th0, CD4, helper T cells (Th cells
Original languageEnglish
Pages (from-to)257-267
JournalImmunology
Volume129
Issue number2
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes