B7-H1 expression on old CD8+ T cells negatively regulates the activation of immune responses in aged animals.
B7-H1 expression on old CD8+ T cells negatively regulates the activation of immune responses in aged animals.
复制标题
旧CD8+ T细胞上的B7-H1表达对老年动物的免疫反应的激活负调节。
DOI：
10.4049/jimmunol.0903561
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Lustgarten J
中科院分区：
文献类型：
--
作者：
Mirza N;Duque MA;Dominguez AL;Schrum AG;Dong H;Lustgarten J
T细胞反应在老年人中受损。B7-CD28家族受体在免疫反应的调节中起关键作用。我们评估了b7家族和cd28家族受体在年轻和年老小鼠的树突状细胞、巨噬细胞、CD4+和CD8+ T细胞中是否存在差异表达，这可能有助于老年小鼠的免疫功能障碍。尽管大多数受体在所有细胞中表达相同，但85%的老年幼稚CD8+ T细胞表达B7-H1，而年轻细胞表达B7-H1的比例为25%。考虑到B7-H1负向调节免疫应答，我们假设B7-H1的表达会下调老CD8+ T细胞的功能。老年CD8+ T细胞的增殖能力降低，但阻断B7-H1可使老年CD8+ T细胞的增殖能力恢复到与年轻CD8+ T细胞相似的水平。体内阻断B7-H1恢复了对B7-H1−bm -185增强的GFP肿瘤的抗肿瘤反应，因此老年动物的反应效率与年轻小鼠相同。我们的数据还表明，与年轻的CD8+ T细胞相比，老年CD8+ T细胞表达的TCR水平较低。然而，在存在B7-H1阻断的抗原刺激下，TCR表达水平在老CD8+ T细胞中恢复，这与更强的T细胞活化相关。这些研究表明，B7-H1在老年CD8+ T细胞中的表达会损害这些细胞的正常激活，并且阻断B7-H1可能是最佳刺激老年CD8 T细胞反应的关键。
T cell responses are compromised in the elderly. The B7-CD28 family receptors are critical in the regulation of immune responses. We evaluated whether the B7-family and CD28-family receptors were differentially expressed in dendritic cells, macrophages, and CD4+ and CD8+ T cells from young and old mice, which could contribute to the immune dysfunction in the old. Although most of the receptors were equally expressed in all cells, >85% of the old naive CD8+ T cells expressed B7-H1 compared with 25% in the young. Considering that B7-H1 negatively regulates immune responses, we hypothesized that expression of B7-H1 would down-regulate the function of old CD8+ T cells. Old CD8+ T cells showed reduced ability to proliferate, but blockade of B7-H1 restored the proliferative capacity of old CD8+ T cells to a level similar to young CD8+ T cells. In vivo blockade of B7-H1 restored antitumor responses against the B7-H1− BM-185–enhanced GFP tumor, such that old animals responded with the same efficiency as young mice. Our data also indicate that old CD8+ T cells express lower levels of TCR compared with young CD8+ T cells. However, following antigenic stimulation in the presence of B7-H1 blockade, the levels of TCR expression were restored in old CD8+ T cells, which correlated with stronger T cell activation. These studies demonstrated that expression of B7-H1 in old CD8+ T cells impairs the proper activation of these cells and that blockade of B7-H1 could be critical to optimally stimulate a CD8 T cell response in the old.
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