IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines
IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines
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DOI：
10.1189/jlb.0109046
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发表时间：
2009-08-01
影响因子：
5.5
通讯作者：
Santamaria, Manuel
中科院分区：
文献类型：
--
作者：
Ortega, Consuelo;Fernandez-A, Silvia;Santamaria, Manuel
产生IL-17的CD 4（+）T淋巴细胞（Th 17）目前被认为是银屑病皮损发病机制的相关参与者。然而，对产生IL-17的CD 8（+）T细胞的潜在作用知之甚少，这些细胞也存在于银屑病斑块中。我们已经解决了银屑病患者的T淋巴细胞的CD 8（+）亚型的功能特征。我们的研究结果表明，银屑病炎症皮肤组织中的CD 8（+）IL-17（+）细胞有效地产生TNF-α和IFN-γ（Th 1相关细胞因子）以及IL-17、IL-21和IL-22（Th 17相关细胞因子）。还观察到RORC转录因子的显著上调。这些细胞对TGFAP不敏感，但对抗CD 3/CD 28刺激显示出增殖反应，IL-12和IL-15可增强这种反应。阻断TNF-α活性可抑制TCR介导的活化和IL-17的产生。CD 8（+）IL-17（+）T细胞是细胞毒性细胞，其显示TCR/CD 3介导的细胞毒性能力以杀死靶细胞。因此，CD 8（+）IL-17（+）T细胞与Th 17细胞具有一些关键特征，并表现出归因于T淋巴细胞的CD 8（+）谱系的显著分化能力，为人类表皮产生IL-17的细胞的功能资源提供了新的见解，这可能对我们理解银屑病的发病机制具有潜在的意义。J. Leukoc. 86：435-443; 2009.
IL-17-producing CD4(+) T lymphocytes (Th17) are currently considered relevant participants in the pathogenesis of psoriasis skin lesions. However, little is known about the potential role of IL-17-producing CD8(+) T cells, which are also present at the psoriatic plaque. We have addressed the functional characterization of this CD8(+) subtype of T lymphocytes from psoriasis patients. Our results show that CD8(+)IL-17(+) cells from psoriasis-inflamed skin tissue produce TNF-alpha and IFN-gamma (Th1-related cytokines) as well as IL-17, IL-21, and IL-22 (Th17-related cytokines) efficiently. A significant up-regulation of the RORC transcription factor is also observed. These cells are refractory to Tregs but show a proliferative response to anti-CD3/CD28 stimulation that is enhanced by IL-12 and IL-15. Blocking of TNF-alpha activity inhibits TCR-mediated activation and IL-17 production. CD8(+)IL-17(+) T cells are cytotoxic cells that display TCR/CD3-mediated cytotoxic abilities to kill target cells. Thus, CD8(+)IL-17(+) T cells share some key features with Th17 cells and exhibit remarkable differential abilities attributable to the CD8(+) lineage of T lymphocytes, adding new insights into the functional resources of IL-17-producing cells from human epidermis that could be of potential interest to our understanding of the pathogenesis of psoriasis. J. Leukoc. Biol. 86: 435-443; 2009.