Published online before print December 19, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0305130

Received for publication March 9, 2005.
Revised April 13, 2005.
Accepted for publication October 21, 2005.

Article

Involvement of CCR5 in the passage of Th1-type cells across the blood-retina barrier in experimental autoimmune uveitis

Isabel J. Crane ^*@, Heping Xu ^*, Carol Wallace ^*, Ayyakkannu Manivannan , Matthias Mack , Janet Liversidge ^*, Gabriel Marquez , Peter F. Sharp , and John V. Forrester ^*

Departments of *Ophthalmology and Bio-Medical Physics and Bio-Engineering, University of Aberdeen Medical School, Foresterhill, United Kingdom; Department of Internal Medicine II, University of Regensburg, Germany; and Centro Nacional de Biotecnologia, UAM-Campus de Cantoblanco, Madrid, Spain

^@ To whom correspondence should be addressed. E-mail: i.j.crane{at}abdn.ac.uk.

Abstract

Although the recruitment of T helper cell type 1 (Th1)/Th2 cells into peripheral tissues is essential for inflammation and the host response to infection, the traffic signals that enable the distinct positioning of Th1/Th2 cells are unclear. We have determined the role of CC chemokine receptor 5 (CCR5) in this using experimental autoimmune uveitis (EAU) as a model system. In EAU, Th1-like cells are preferentially recruited into the retina across the blood-retina barrier, partly as a result of expression of the adhesion molecules P-selectin glycoprotein ligand 1 and lymphocyte function-associated antigen-1 on these cells. CD3⁺ T cells, infiltrating the retina, also expressed the chemokine receptor CCR5, and CCR5 ligands, macrophage-inflammatory protein-1 (MIP-1), MIP-1, and regulated on activation, normal T expressed and secreted, were strongly expressed in the retina at peak EAU. Th1-like cells, polarized in vitro, expressed high levels of CCR5. The trafficking of these CCR5⁺ cells was examined by tracking them after adoptive transfer in real time in vivo at an early disease stage using scanning laser ophthalmoscopy. Treatment of the cells with antibody against CCR5 prior to transfer resulted in a reduction in their infiltration into the retina. However, rolling velocity, rolling efficiency, and adherence of the cells to retinal endothelium were not reduced. CCR5 is clearly important for Th1 cell recruitment, and this study demonstrates for the first time in vivo that CCR5 may act at the level of transendothelial migration rather than at the earlier stage of rolling on the endothelium.

Key Words: chemokines • chemokine receptor • cell trafficking • inflammation

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