CD4~+ T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by Galpha_i coupled receptors but is CCR6- and CXCR3-independent

摘要

Summary: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 chemoldne 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 Galpha_i coupled receptors, to which chemoldne 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.