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 language | English (US) |
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Pages (from-to) | 1675-1686 |
Number of pages | 12 |
Journal | Journal of Clinical Investigation |
Volume | 110 |
Issue number | 11 |
DOIs | |
State | Published - Dec 2002 |
Externally published | Yes |
ASJC Scopus subject areas
- Medicine(all)