Seino K, Azuma M, Bashuda H, Fukao K, Yagita H, Okumura K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Int Immunol. 1995 Aug;7(8):1331-7. doi: 10.1093/intimm/7.8.1331.
In vascularized organ transplantation, vascular endothelial cells (EC) confronting recipient T cells are potentially significant APC initiating cellular immune responses that lead to rejection. In the present study, we studied the ability of human EC to stimulate allogeneic T cells and the co-stimulatory molecules involved in this response. On both human umbilical vein endothelial cells (HUVEC) and microvascular endothelial cells (MVEC), MHC class I, intercellular adhesion molecule (ICAM)-1 and CD86 were constitutively expressed as assessed by flow cytometry. After IFN-gamma treatment, MHC class II expression was induced, and MHC class I and ICAM-1 were up-regulated. In contrast, the expression of CD86 was unchanged and CD80 was undetectable even after IFN-gamma treatment. Highly purified CD4+ T cells proliferated in response to IFN-gamma-treated allogeneic HUVEC and MVEC, and this response was efficiently blocked by mAb to MHC class II, ICAM-1 and CD86. Furthermore, the addition of anti-CD86 mAb to the primary culture with allogeneic EC resulted in the induction of alloantigen-specific anergy. These results suggest that CD86 expressed on EC plays a critical role in initiating cellular immune responses to vascularized allografts and would be an important target for immune intervention.
在血管化器官移植中，与受体T细胞接触的血管内皮细胞（EC）可能是引发细胞免疫反应导致排斥的重要抗原呈递细胞（APC）。在本研究中，我们研究了人EC刺激同种异体T细胞的能力以及参与该反应的共刺激分子。通过流式细胞术评估，人脐静脉内皮细胞（HUVEC）和微血管内皮细胞（MVEC）上均组成性表达MHC I类分子、细胞间黏附分子（ICAM）-1和CD86。经γ干扰素处理后，诱导了MHC II类分子的表达，且MHC I类分子和ICAM-1上调。相反，即使经γ干扰素处理后，CD86的表达未改变，且未检测到CD80。高度纯化的CD4 + T细胞对经γ干扰素处理的同种异体HUVEC和MVEC产生增殖反应，且该反应被抗MHC II类分子、ICAM-1和CD86的单克隆抗体有效阻断。此外，在与同种异体EC的原代培养中加入抗CD86单克隆抗体可诱导同种抗原特异性无反应性。这些结果表明，EC上表达的CD86在引发对血管化同种异体移植物的细胞免疫反应中起关键作用，并且将是免疫干预的重要靶点。
