CTLA-4+ CD8+ T cells that encounter B7-2+ iris pigment epithelial cells express their own B7-2 to achieve global suppression of T cell activation
CTLA-4+ CD8+ T cells that encounter B7-2+ iris pigment epithelial cells express their own B7-2 to achieve global suppression of T cell activation
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DOI：
10.4049/jimmunol.172.7.4184
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Streilein, JW
中科院分区：
文献类型：
--
作者：
Sugita, S;Ng, TF;Streilein, JW
体外培养的眼色素上皮细胞具有抑制tcr依赖性T细胞活化的新特性。虹膜PE （IPE）细胞通过直接细胞接触机制实现这种抑制，其中PE细胞表达的B7-2与应答T细胞上的CTLA-4相互作用。由于CTLA-4的表达在很小比例的初始脾T细胞上构成性表达，并且由于脾T细胞暴露于IPE会导致全局T细胞抑制，因此我们研究了实现抑制的机制。利用CD80 （B7-1）、CD86 （B7-2）、CTLA-4和/或CD28基因被破坏的供体小鼠的脾T细胞和IPE，我们报道了B7-2(+) IPE在抗cd3存在下选择性地支持CTLA-4(+) CD8(+) T细胞的激活，这些T细胞表达自身的B7-2并分泌更多的活性tgf - β。相比之下，ctla -4阴性T细胞的活化，特别是CD4（+）细胞，在这些培养中被严重抑制。由于在这些培养中，只有当IPE和T细胞都拥有B7-2基因并将共刺激物作为表面分子表达时，才能获得T细胞活化的全局抑制，因此我们提出，在眼睛（免疫特权部位）实质细胞存在下激活的T细胞表达B7-2，从而使它们能够抑制旁观者T细胞。因此，B7-2在T细胞上的表达参与了它们在体外作为调节因子的最终能力。
Pigment epithelial (PE) cells cultured from the eye possess the novel property of suppressing TCR-dependent activation of T cells in vitro. Iris PE (IPE) cells accomplish this suppression by a direct cell contact mechanism in which B7-2 expressed by the PE cells interacts with CTLA-4 on responding T cells. Because CTLA-4,expression is constitutively expressed on a very small proportion of naive splenic T cells and since exposure of splenic T cells to IPE leads to global T cell suppression, we have inquired into the mechanism by which suppression is achieved. Using splenic T cells and IPE from donor mice with disrupted genes for CD80 (B7-1), CD86 (B7-2), CTLA-4, and/or CD28, we report that B7-2(+) IPE in the presence of anti-CD3 supported selectively the activation of CTLA-4(+) CD8(+) T cells that express their own B7-2 and secrete enhanced amounts of active TGFbeta. By contrast, activation of CTLA-4-negative T cells, especially CD4(+) cells, in these cultures was profoundly suppressed. Because global suppression of T cell activation in these cultures was obtained only when both IPE and T cells possessed B7-2 genes and expressed the costimulators as surface molecules, we propose that T cells activated in the presence of parenchymal cells from the eye (an immune privileged site) express B7-2 in a manner that equips them to suppress bystander T cells. Thus, B7-2 expression on T cells participates in their eventual ability to function as regulators in vitro.