Affordable Access

CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC.

Authors
  • Denning, Timothy L
  • Qi, Hai
  • König, Rolf
  • Scott, Kevin G
  • Naganuma, Makoto
  • Ernst, Peter B
Type
Published Article
Journal
Journal of immunology (Baltimore, Md. : 1950)
Publication Date
Sep 01, 2003
Volume
171
Issue
5
Pages
2279–2286
Identifiers
PMID: 12928372
Source
Medline
License
Unknown

Abstract

Regulatory CD4+ Th cells can prevent many autoimmune diseases; however, the factors selecting for these cells remain poorly defined. In transgenic mice with a mutation in the CD4 binding region on class II MHC, the disruption of CD4-class II interactions selected for CD4+ Th cells that expressed surface markers and cytokines associated with regulatory Th cells. Th cells from these mice were enriched for CD45RB(low) as well as CD25+, while they expressed high levels of the transcription factor associated with regulatory T cells, Foxp3, and cytokines, including IL-4, IL-10, and IFN-gamma mRNA and protein. These regulatory Th cells inhibited the function of APCs via IL-10 production, and adoptive transfer of these cells prevented weight loss and inflammation in a model of colitis. CD4+ regulatory Th cells emerged only when interactions between CD4 and class II MHC were deficient on cells of nonhemopoietic origin. These data support a novel model controlling the differentiation of regulatory Th cells and suggest that interactions between CD4 and class II MHC may a useful target for re-educating T cells as a treatment for inflammatory diseases.

Report this publication

Statistics

Seen <100 times