Methe Heiko, Hess Shmuel, Edelman Elazer R
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Semin Immunol. 2008 Apr;20(2):117-22. doi: 10.1016/j.smim.2007.12.005. Epub 2008 Feb 19.
The endothelium is a unique immunologic target. The first host-donor reaction in any cell, tissue or organ transplant occurs at the blood-tissue interface, the endothelium. When endothelial cells are themselves the primary component of the implant a second set of immunologic reactions arises. Injections of free endothelial cell implants elicit a profound major histocompatibility complex (MHC) II dominated immune response with significant sensitivity, cascade enhancement and immune memory. Endothelial cells embedded within three-dimensional matrices retain all the biosecretory capacity of quiescent endothelial cells. Perivascular implants of such cells are the most potent inhibitor of intimal hyperplasia and thrombosis following controlled vascular injury, but without any immune reactivity. Allo- and even xenogeneic endothelial cells evoke no significant humoral or cellular immune response in immunocompetent hosts when embedded within matrices. Moreover, endothelial implants are immunomodulatory, reducing the extent of the memory response to previous free cell implants. Attenuated immunogenicity results in muted activation of adaptive and innate immune cells. These findings point toward a pivotal role of matrix-cell-interconnectivity for the cellular immune phenotype and might therefore assist in the design of extracellular matrix components for successful tissue engineering.
内皮细胞是一个独特的免疫靶点。在任何细胞、组织或器官移植中，首次宿主 - 供体反应发生在血液 - 组织界面，即内皮细胞处。当内皮细胞本身是植入物的主要成分时，就会出现另一组免疫反应。注射游离的内皮细胞植入物会引发以主要组织相容性复合体（MHC）II为主导的强烈免疫反应，具有显著的敏感性、级联增强和免疫记忆。嵌入三维基质中的内皮细胞保留了静止内皮细胞的所有生物分泌能力。此类细胞的血管周围植入物是控制血管损伤后内膜增生和血栓形成的最有效抑制剂，但没有任何免疫反应性。当同种异体甚至异种内皮细胞嵌入基质中时，在免疫活性宿主中不会引发明显的体液或细胞免疫反应。此外，内皮植入物具有免疫调节作用，可降低对先前游离细胞植入物的记忆反应程度。免疫原性减弱导致适应性和先天性免疫细胞的激活减弱。这些发现表明基质 - 细胞相互连接对于细胞免疫表型起着关键作用，因此可能有助于设计用于成功组织工程的细胞外基质成分。
