期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 36, 期 9, 页码 1910-1918出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.116.308039
关键词
allograft; antigen-presenting cells; chemotaxis; endothelial cell; lymphocyte
资金
- National Institutes of Health [R01-HL051014]
Objective Circulating human T effector memory cell (T-EM) recognition of nonself MHC (major histocompatibility complex) molecules on allograft endothelial cells can initiate graft rejection despite elimination of professional antigen-presenting cells necessary for naive T-cell activation. Our previous studies of CD4 T-EM have established that engagement of the T-cell receptor not only activates T cells but also triggers transendothelial migration (TEM) by a process that is distinct from that induced by activating chemokine receptors on T cells, being slower, requiring microtubule-organizing center-directed cytolytic granule polarization to and release from the leading edge of the T cell, and requiring engagement of proteins of the endothelial cell lateral border recycling compartment. Although CD4 T-EM may contribute to acute allograft rejection, the primary effectors are alloreactive CD8 T-EM. Whether and how T-cell receptor engagement affects TEM of human CD8 T-EM is unknown. Approach and Results We modeled TEM of CD8 T-EM across cultured human microvascular endothelial cells engineered to present superantigen under conditions of venular shear stress in vitro in a flow chamber. Here, we report that T-cell receptor engagement can also induce TEM of this population that similarly differs from chemokine receptor-driven TEM with regard to kinetics, morphological manifestations, and microtubule-organizing center dynamics as with CD4 T-EM. However, CD8 T-EM do not require either cytolytic granule release or interactions with proteins of the lateral border recycling compartment. Conclusions These results imply that therapeutic strategies designed to inhibit T-cell receptor-driven recruitment based on targeting granule release or components of the lateral border recycling compartment will not affect CD8 T-EM and are unlikely to block acute rejection in the clinic.
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