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.
abstract: 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(+) CD62L(low) MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4(+) CD62L(low) 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(+) CD62L(low) cell migration to the large intestinal mucosa during T. muris infection.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK. Marcus.Svensson@med.lu.se
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson
authors.forename: Karen
authors.initials: K
authors.lastname: Russell
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D044385:GTP-Binding Protein alpha Subunits / Q000276:immunology / Q000378:metabolism*; D018928:Immunity, Mucosal / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D037342:Pertussis Toxin / Q000494:pharmacology; D054399:Receptors, CCR6 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D014257:Trichuriasis / Q000276:immunology* / Q000473:pathology; D014258:Trichuris / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D019138:Antibodies, Blocking; C498126:CCR6 protein, mouse; C515188:Cxcr3 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D037342:Pertussis Toxin