Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, S709 BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Immunol Lett. 2018 Mar;195:55-60. doi: 10.1016/j.imlet.2017.10.002. Epub 2017 Oct 5.
Despite long-standing recognition of the importance of T cells in systemic sclerosis (SSc; scleroderma), the role of CD8 T cells in disease pathogenesis has not been well studied. Our work has shown that over-production of the pro-fibrotic cytokine IL-13 by peripheral blood effector/memory CD8 T cells is critical for predisposing patients to more severe forms of cutaneous fibrosis. Moreover, IL-13-producing CD8 T cells induce a pro-fibrotic phenotype in normal and SSc dermal fibroblasts, and exhibit a strong cytotoxic activity ex vivo. We also found that CD8 T cells are predominantly abundant in the skin lesions of patients in the early stages of diffuse cutaneous (dc)SSc compare to late-stage disease patients. Isolation of CD8 T cells from the lesional skin of early active dcSSc patients, established that they are skin-resident, express cytolytic molecules and co-express extremely high levels of IL-13 and IFNγ. Other recent studies corroborate these findings and together strongly suggest that CD8 T cells contribute to SSc pathogenesis through the production of high levels of cytokines with pro-inflammatory and pro-fibrotic function as well as by exhibiting a cytotoxic activity.
尽管人们早就认识到 T 细胞在系统性硬化症（SSc；硬皮病）中的重要性，但 CD8 T 细胞在疾病发病机制中的作用尚未得到很好的研究。我们的工作表明，外周血效应/记忆 CD8 T 细胞过度产生促纤维化细胞因子 IL-13 对于使患者易患更严重形式的皮肤纤维化至关重要。此外，产生 IL-13 的 CD8 T 细胞可诱导正常和 SSc 真皮成纤维细胞产生促纤维化表型，并具有很强的体外细胞毒性活性。我们还发现，与晚期疾病患者相比，CD8 T 细胞在弥漫性皮肤型（dc）SSc 早期患者的皮肤损伤中更为丰富。从早期活动性 dcSSc 患者的皮损中分离出 CD8 T 细胞，证实它们是皮肤驻留细胞，表达细胞毒性分子，并共同表达极高水平的 IL-13 和 IFNγ。其他最近的研究证实了这些发现，并强烈表明 CD8 T 细胞通过产生具有促炎和促纤维化功能的高水平细胞因子以及表现出细胞毒性活性来促进 SSc 的发病机制。
