期刊
JOURNAL OF IMMUNOLOGY
卷 187, 期 3, 页码 1432-1439出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100299
关键词
-
类别
资金
- Biotechnology and Biological Sciences Research Board
- AstraZeneca
- MRC [G9818340] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/B/01057] Funding Source: researchfish
- British Heart Foundation [PG/09/069/27905] Funding Source: researchfish
- Medical Research Council [G9818340B, G9818340] Funding Source: researchfish
Memory lymphocytes support inflammatory and immune responses. To do this, they enter tissue via blood vascular endothelial cells (BVEC) and leave tissue via lymphatic vascular endothelial cells (LVEC). In this study, we describe a hierarchy of signals, including novel regulatory steps, which direct the sequential migration of human T cells across the blood and the lymphatic EC. Cytokine-stimulated (TNF and IFN) human BVEC preferentially recruited memory T cells from purified PBL. Lymphocyte recruitment from flow could be blocked using a function-neutralizing Ab against CXCR3. However, a receptor antagonist directed against the PGD(2) receptor DP2 (formerly chemoattractant receptor-homologous molecule expressed on Th2 cells) inhibited transendothelial migration, demonstrating that the sequential delivery of the chemokine and prostanoid signals was required for efficient lymphocyte recruitment. CD4(+) T cells recruited by BVEC migrated with significantly greater efficiency across a second barrier of human LVEC, an effect reproduced by the addition of exogenous PGD(2) to nonmigrated cells. Migration across BVEC or exogenous PGD(2) modified the function, but not the expression, of CCR7, so that chemotaxis toward CCL21 was significantly enhanced. Thus, chemokines may not regulate all stages of lymphocyte migration during inflammation, and paradigms describing their trafficking may need to account for the role of PGD(2). The Journal of Immunology, 2011, 187: 1432-1439.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据