Platzer Hadrian, Trauth Richard, Nees Timo A, Tripel Elena, Gantz Simone, Schiltenwolf Marcus, Moradi Babak, Rosshirt Nils
Clinic for Orthopedic and Trauma Surgery, University Hospital Heidelberg, 69118 Heidelberg, Germany.
Clinic for Orthopedics and Trauma Surgery, University Hospital Kiel, 24105 Kiel, Germany.
J Clin Med. 2022 May 17;11(10):2814. doi: 10.3390/jcm11102814.
Osteoarthritis (OA) is no longer considered a purely degenerative disease. OA is defined as a disease of the entire joint, in which inflammation occurs in various joint tissues. The overall aim of this study was to analyze the presence and polarization of CD8 T cell subsets in OA knee joints, in relation to the OA stage and compartment (synovial fluid (SF), synovial membrane (SM,) peripheral blood (PB)). A quantitative flow analysis of CD8 T cell subsets to compare the SF, SM, PB, was performed in patients with different stages of OA (early, unicondylar and bicondylar OA). Samples of the SF, SM and PB were harvested from a total of 55 patients at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Uni- and bicondylar OA was confirmed and graded by two plane radiographs. Samples were analyzed by flow cytometry for surface markers, and cytokines by intracellular staining (ICS). CD8 T cells were shown to be differentiated into pro-inflammatory IFN-γ producing Tc1 and IL-17A producing Tc17, as well as anti-inflammatory IL-4 producing Tc2. All CD8 T cell subsets (Tc1, Tc17, and Tc2) were detected in both the SM and SF. The percentage of CD8 T cell subsets of the total CD8 T cell population was dependent on the OA stage and compartment. Compared with the peripheral blood (PB), the proportion of CD8IFN-γ Tc1 and CD8IL-17A Tc17 was significantly increased in OA SF. This was confirmed in our data for both early OA and end-stage OA. In the SM samples of end-stage OA patients, the proportion of CD8IL-17A Tc17 was significantly increased compared to the PB. Comparing SF and SM samples of end-stage OA patients, the proportion of CD8IFN-γ Tc1 was significantly increased in SF, whereas there were no differences concerning CD8IL-4 Tc2 and CD8IL-17A Tc17. End-stage OA samples showed a significant increase of CD8IL-4 Tc2 in the SM for both unicondylar and bicondylar OA compared to early OA. CD8 T cells infiltrating the SM and SF in OA knees are differentiated into IFN-γ-, IL-17A-, and IL-4-producing CD8 T cell subsets (Tc1, Tc17, Tc2). This differentiation depends on the OA stage and OA compartment. Further investigation of CD8 T cell subsets and their interaction with other inflammatory cells such as CD4 T cells and macrophages may help to identify novel therapeutic anti-inflammatory strategies for containing OA progression.
骨关节炎（OA）不再被认为是一种单纯的退行性疾病。OA被定义为一种累及整个关节的疾病，其中各种关节组织会发生炎症。本研究的总体目标是分析OA膝关节中CD8 T细胞亚群的存在情况及其极化状态，以及与OA分期和关节腔（滑液（SF）、滑膜（SM）、外周血（PB））的关系。对不同OA分期（早期、单髁和双髁OA）患者的SF、SM、PB中的CD8 T细胞亚群进行定量流式分析以作比较。在手术时从总共55例患者中采集SF、SM和PB样本。早期OA由独立的外科医生在术中确认。单髁和双髁OA通过双平面X线片确认并分级。样本通过流式细胞术分析表面标志物，并通过细胞内染色（ICS）分析细胞因子。CD8 T细胞可分化为产生促炎细胞因子IFN-γ的Tc1和产生IL-17A的Tc17，以及产生抗炎细胞因子IL-4的Tc2。在SM和SF中均检测到所有CD8 T细胞亚群（Tc1、Tc17和Tc2）。总CD8 T细胞群体中CD8 T细胞亚群的百分比取决于OA分期和关节腔。与外周血（PB）相比，OA滑液中CD8IFN-γ Tc1和CD8IL-17A Tc17的比例显著增加。这在我们关于早期OA和终末期OA的数据中均得到证实。在终末期OA患者的SM样本中，与PB相比，CD8IL-17A Tc17的比例显著增加。比较终末期OA患者的SF和SM样本，SF中CD8IFN-γ Tc1的比例显著增加，而CD8IL-4 Tc2和CD8IL-17A Tc17没有差异。与早期OA相比，终末期OA样本在单髁和双髁OA的SM中CD8IL-4 Tc2均显著增加。浸润OA膝关节SM和SF的CD8 T细胞分化为产生IFN-γ、IL-17A和IL-4的CD8 T细胞亚群（Tc1、Tc17、Tc2）。这种分化取决于OA分期和OA关节腔。进一步研究CD8 T细胞亚群及其与其他炎症细胞如CD4 T细胞和巨噬细胞的相互作用，可能有助于确定控制OA进展的新型抗炎治疗策略。
