CCR4-bearing T cells participate in autoimmune diabetes.
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.
Kim
Soon H
SH
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Cleary
Mary M
MM
Fox
Howard S
HS
Chantry
David
D
Sarvetnick
Nora
N
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011236:Prediabetic State / Q000276:immunology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C515355:Ccr4 protein, mouse; D054398:Receptors, CCR4; D019707:Receptors, Chemokine