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

Timothy L. Denning, Hai Qi, Rolf König, Kevin G. Scott, Makoto Naganuma, Peter B. Ernst

Research output: Contribution to journalArticle

19 Scopus citations

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 CD45RBlow 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-γ 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.

Original languageEnglish (US)
Pages (from-to)2279-2286
Number of pages8
JournalJournal of Immunology
Volume171
Issue number5
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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