Human vascular endothelial cells stimulate memory but not naive CD8+ T cells to differentiate into CTL retaining an early activation phenotype
Human vascular endothelial cells stimulate memory but not naive CD8+ T cells to differentiate into CTL retaining an early activation phenotype
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DOI：
10.4049/jimmunol.164.10.5146
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发表时间：
2000-05-15
影响因子：
4.4
通讯作者：
Pober, JS
中科院分区：
文献类型：
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作者：
Dengler, TJ;Pober, JS
内皮细胞（EC）选择性同种异体反应性CTL可介导同种异体免疫性血管损伤。在本研究中，将纯化的人CD 8（+）T细胞与同种异体EC共培养，产生EC选择性CTL，并与针对相应的B淋巴母细胞样细胞（BLC）的常规CTL进行比较，EC引起记忆而非幼稚CD 8（+）T细胞的激活和扩增，其分化为保留高表面表达的CD 69、CD 25、和CD 62 L，并显示低细胞内穿孔素含量。相反，BLC刺激的CTL可以从初始或记忆性CD 8（+）T细胞产生，并显示出更成熟的表型（低CD 69、CD 25和CD 62 L，具有更高水平的穿孔素）。EC刺激的同种异体反应性T细胞扩增的有效性比相应的BLC刺激的培养物低5- 20倍，这是单个微培养物的可测定细胞毒性降低的原因。在这些IL-2补充的共培养物中，通过单克隆抗体阻断LFA-3、ICAM-1或CD 40提供的共刺激，通过加入共致抗CD 28单克隆抗体，或通过用CD 40配体预活化EC，未观察到对CTL产生或表型的影响。环孢素抑制CTL扩增和细胞毒性类似EC和BLC刺激的文化，但不影响那些CTL的表型出现。这项研究扩展了内皮细胞作为不同于传统APC的免疫调节细胞类型的表征，并可以解释为什么动脉内膜内的移植物排斥反应，其中EC可能是APC的主要类型的解剖隔室，是可分离的移植物实质中的排斥反应。
Endothelial cell (EC)-selective alloreactive CTL may mediate alloimmune vascular injury. In the present study, EC-selective CTL were generated in cocultures of purified human CD8(+) T cells with allogeneic EC and were compared with conventional CTL against corresponding B lymphoblastoid cells (BLC), EC caused activation and expansion of memory but not naive CD8(+) T cells, which differentiated into EC-selective CTL that retained high surface expression of CD69, CD25, and CD62L and displayed low intracellular perforin content. In contrast, BLC-stimulated CTL could be generated from naive or memory CD8(+) T cells and showed a more mature phenotype (low CD69, CD25, and CD62L with higher levels of perforin), The expansion of alloreactive T cells by EC stimulation was 5- to 20-fold less effective than in corresponding BLC-stimulated cultures, accounting for a reduction in the assayable cytotoxicity of individual microcultures. In these IL-2-supplemented cocultures, no effect on CTL generation or phenotype was observed by mAb blocking of costimulation provided by LFA-3, ICAM-1, or CD40, by addition of comitogenic anti-CD28 mAb, or by preactivation of EC with CD40 ligand. Cyclosporine inhibited CTL expansion and cytotoxicity similarly in both EC- and BLC-stimulated cultures but did not affect the phenotype of those CTL that did emerge. This study extends the characterization of endothelium as an immunoregulatory cell type distinct from conventional APC and may explain why graft rejection within the arterial intima, an anatomic compartment in which EC may be the primary type of APC, is separable from rejection in the graft parenchyma.