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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

helminths

mucosal immunity

trafficking

receptors

chemokine

Th17)

Th3

Th2

Th1

Th0

CD4

helper T cells (Th cells

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)