TY - JOUR
T1 - Involvement of CCR5 in the passage of Th-1-type cells across the blood-retina barrier in experimental autoimmune uveitis
AU - Crane, Isabel Joan
AU - Xu, Heping
AU - Wallace, Carol Ann
AU - Manivannan, Ayyakkannu
AU - Mack, M.
AU - Liversidge, Janet Mary
AU - Marquez, G.
AU - Sharp, Peter Frederick
AU - Forrester, John Vincent
PY - 2006/3
Y1 - 2006/3
N2 - Although the recruitment of T helper cell type I (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 antoimmune 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 I 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 alpha (MIP-1 alpha), MIP-1 beta, and regulated on activation, normal T expressed and secreted (RANTES), 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.
AB - Although the recruitment of T helper cell type I (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 antoimmune 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 I 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 alpha (MIP-1 alpha), MIP-1 beta, and regulated on activation, normal T expressed and secreted (RANTES), 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.
KW - chemokines
KW - chemokine receptor
KW - cell trafficking
KW - inflammation
KW - CHEMOKINE RECEPTOR EXPRESSION
KW - IN-VIVO
KW - CUTTING EDGE
KW - TH1 CELLS
KW - LEUKOCYTE TRAFFICKING
KW - T-HELPER-2 CELLS
KW - UP-REGULATION
KW - T-CELLS
KW - MIGRATION
KW - RECRUITMENT
U2 - 10.1189/jlb.0305130
DO - 10.1189/jlb.0305130
M3 - Article
SN - 0741-5400
VL - 79
SP - 435
EP - 443
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -