The interleukin-8 receptor B and CXC chemokines can mediate transendothelial migration of human skin homing T cells

被引:41
作者
Babi, LFS
Moser, B
Soler, MTP
Moser, R
Loetscher, P
Villiger, B
Blaser, K
Hauser, C
机构
[1] SWISS INST ALLERGY & ASTHMA RES,CH-7270 DAVOS,SWITZERLAND
[2] UNIV BERN,THEODOR KOCHER INST,BERN,SWITZERLAND
[3] SWISS FED INST TECHNOL,DEPT PHARM,ZURICH,SWITZERLAND
[4] THURGAUISCH SCHAFFHAUS HOHENKLIN,DAVOS,SWITZERLAND
[5] UNIV HOSP GENEVA,DIV IMMUNOL & ALLERGOL,ALLERGY UNIT,GENEVA,SWITZERLAND
[6] UNIV HOSP GENEVA,DEPT DERMATOL,GENEVA,SWITZERLAND
关键词
skin homing T cell; interleukin-8 receptor B; interleukin-8; transendothelial migration; CXC chemokines;
D O I
10.1002/eji.1830260914
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We studied the involvement of chemokines that bind to G protein-coupled receptors in the migration of skin homing T cells across a bilayer vascular construct (BVC) consisting of a fibroblast matrix underneath an activated endothelial (EC) monolayer. Based on the expression of the cutaneous lymphocyte-associated antigen (CLA). a skin homing receptor, CD45R0(+) T cells freshly isolated from blood or HUT-78 cutaneous T lymphoma cells were separated into CLA(+) and CLA(-) subpopulations. These T cells were incubated on interleukin (IL)-1 beta and tumor necrosis factor-alpha-activated EC, and the number of transmigrated cells was determined. The chemokine IL-8 was selectively involved in the enhanced migration of CLA(+) T cells across activated EC as demonstrated by blocking antibody to IL-8 but not to GRO-alpha, MCP-1 and RANTES. Identical results were obtained with both human umbilical vein EC (HUVEC) and microvascular skin EC (HDMEC). Pertussis toxin selectively inhibited the enhanced transendothelial migration (TEM) of CLA(+) T cells, suggesting that CLA-dependent TEM depends on Gi protein-transmitted signals. Moreover, the IL-8 receptor B (IL-8RB) appeared to be functionally involved in TEM, as demonstrated by receptor desensitization with the CXC chemokines IL-8 and GRO-alpha and by blocking the IL-8RB with specific monoclonal antibodies. Although only the IL-8RB was involved in CLA-dependent TEM, mRNA encoding IL-8RA and IL-8RB was expressed by both CLA(+) and CLA(-) T cells. This correlated with IL-8RA and IL-8RB surface expression on these cells. Thus, the IL-8RB is selectively functional in TEM of T cells expressing the skin homing receptor CLA. Our results demonstrate a critical role for IL-8 and possibly other IL-8RB ligands in addition to the IL-8RB in TEM and suggest the involvement of these molecules in the homing of specific T cells to inflamed skin.
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页码:2056 / 2061
页数:6
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