Document Type

Article

Journal Title

The Journal of clinical investigation

Publication Date

12-1-2002

Volume

110

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.

MeSH Headings

Animals, Diabetes Mellitus, Type 1, Immunologic Memory, Immunophenotyping, Islets of Langerhans, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Prediabetic State, Receptors, CCR4, Receptors, Chemokine, T-Lymphocytes

ISSN

0021-9738

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