Human CD5 protects circulating tumor antigen-specific CTL from tumor-mediated activation-induced cell death
Human CD5 protects circulating tumor antigen-specific CTL from tumor-mediated activation-induced cell death
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DOI：
10.4049/jimmunol.178.11.6821
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Mami-Chouaib, Fathia
中科院分区：
文献类型：
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作者：
Friedlein, Grzegorz;El Hage, Faten;Mami-Chouaib, Fathia
我们之前从肺癌患者的PBL和肿瘤浸润淋巴细胞中鉴定了几种肿瘤特异性T细胞克隆，它们具有相同的TCR重排和相似的溶解电位，但具有不同的抗肿瘤反应。发现TCR抑制分子CD5的作用损害外周T细胞对肿瘤的反应性参与了这一过程。在本报告中，我们证明CD5还控制特异性T细胞对肿瘤触发的激活诱导细胞死亡（AICD）的易感性。利用表达不同水平CD5的肿瘤浸润淋巴细胞和pbl衍生克隆，我们的研究结果表明，T淋巴细胞对同源肿瘤的AICD反应与CD5的表面表达水平成反比。他们还提出CD5直接参与这一过程，正如用特异性单抗中和CD5分子后肿瘤介导的T淋巴细胞AICD增加所揭示的那样。从机制上讲，我们的数据表明FasL表达的下调和随后的caspase-8激活的抑制与cd5诱导的T细胞存活有关。这些结果为CD5在外周肿瘤特异性T细胞命运中的作用提供了证据，并进一步表明其在调节CTL抗肿瘤反应的扩展方面的作用。
We previously characterized several tumor-specific T cell clones from PBL and tumor-infiltrating lymphocytes of a lung cancer patient with identical TCR rearrangements and similar lytic potential, but with different antitumor response. A role of the TCR inhibitory molecule CD5 to impair reactivity of peripheral T cells against the tumor was found to be involved in this process. In this report, we demonstrate that CD5 also controls the susceptibility of specific T cells to activation-induced cell death (AICD) triggered by the tumor. Using a panel of tumor-infiltrating lymphocytes and PBL-derived clones expressing different levels of CD5, our results indicate that T lymphocyte AICD in response to the cognate tumor is inversely proportional to the surface expression level of CD5. They also suggest a direct involvement of CD5 in this process, as revealed by an increase in tumor-mediated T lymphocyte AICD following neutralization of the molecule with specific mAb. Mechanistically, our data indicate that down-regulation of FasL expression and subsequent inhibition of caspase-8 activation are involved in CD5-induced T cell survival. These results provide evidence for a role of CD5 in the fate of peripheral tumor-specific T cells and further suggest its contribution to regulate the extension of CTL response against tumor.