Abstract

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4+ T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore, enhanced recruitment of CCR4-bearing cells in NOD mice resulting from transgenic expression of MDC resulted in acceleration of clinical disease. Cumulatively, the results demonstrate that CCR4-bearing T cells participate in the development of such tissue-driven autoimmune reactions.

Original languageEnglish (US)
Pages (from-to)1675-1686
Number of pages12
JournalJournal of Clinical Investigation
Volume110
Issue number11
DOIs
StatePublished - Jan 1 2002

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Type 1 Diabetes Mellitus
Chemokine CCL22
T-Lymphocytes
Inbred NOD Mouse
Chemokine CCL17
Chemokine Receptors
T-Lymphocyte Subsets
Disease Progression
Ligands
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

CCR4-bearing T cells participate in autoimmune diabetes. / Kim, Soon H.; Cleary, Mary M.; Fox, Howard S; Chantry, David; Sarvetnick, Nora E.

In: Journal of Clinical Investigation, Vol. 110, No. 11, 01.01.2002, p. 1675-1686.

Research output: Contribution to journalArticle

Kim, Soon H. ; Cleary, Mary M. ; Fox, Howard S ; Chantry, David ; Sarvetnick, Nora E. / CCR4-bearing T cells participate in autoimmune diabetes. In: Journal of Clinical Investigation. 2002 ; Vol. 110, No. 11. pp. 1675-1686.
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