CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression and tissue invasion

N Sarween, A Chodos, M Khan, Chandrabal Raykundalia, AK Abbas, Lucy Walker

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

It is well established that CD4(+)CD25(+) regulatory T cells (Tregs) inhibit autoimmune pathology. However, precisely how the behavior of disease-inducing T cells is altered by Tregs remains unclear. In this study we use a TCR transgenic model of diabetes to pinpoint how pathogenic CD4 T cells are modified by Tregs in vivo. We show that although Tregs only modestly inhibit CD4 cell expansion, they potently suppress tissue infiltration. This is associated with a failure of CD4 cells to differentiate into effector cells and to up-regulate the IFN-gamma-dependent chemokine receptor CXCR-3, which confers the ability to respond to pancreatic islet-derived CXCL10. Our data support a model in which Tregs permit T cell activation, yet prohibit T cell differentiation and migration into Ag-bearing tissues.
Original languageEnglish
Pages (from-to)2942-51
Number of pages10
JournalJournal of Immunology
Volume173
Publication statusPublished - 1 Jan 2004

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