Li Ziping, He Huiwen, Zhang Fujing, Li Haolong, Jin Xianghong, Song Yuhang, Liu Shuangjiao, Wang Xuan, Zhuang Junling
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Medical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Front Immunol. 2024 Sep 17;15:1448653. doi: 10.3389/fimmu.2024.1448653. eCollection 2024.
Broad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.
We tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.
We have found that pronounced lymphopenia and inverted CD4/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.
The prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.
广泛的T细胞表型改变和潜在功能障碍在新冠病毒病（COVID-19）中很突出。关于免疫检查点在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染期间对多发性骨髓瘤（MM）患者T细胞耗竭/激活的作用，数据很少且尚无定论。
我们检测了177例患有COVID-19的MM患者、32例健康感染对照者和42例未感染MM患者的T细胞亚群和免疫检查点。通过流式细胞术评估CD4+和CD8+亚群的百分比以及免疫检查点（程序性死亡受体1（PD-1）、T细胞免疫球蛋白和ITIM结构域（TIGIT）、T细胞免疫球蛋白黏蛋白3（TIM-3）、淋巴细胞活化基因3蛋白（LAG-3）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、肿瘤坏死因子受体超家族成员4（OX40）和4-1BB）。
我们发现，重症COVID-19患者明显的淋巴细胞减少和倒置的CD4/CD8比值在感染后的第一个月内尤其明显。并且T细胞亚群失调在从SARS-CoV-2感染中恢复的重症患者中持续存在。CD4+T细胞上的免疫检查点各不相同，且与适应性免疫水平无关，而CD4+T细胞的比例与体液免疫反应呈正相关。重症患者CD8+T细胞上的PD-1和TIGIT显著升高，并持续超过2个月，这与细胞免疫功能受损有关。此外，免疫治疗患者T细胞上的耗竭分子PD-1和TIGIT减少。
严重SARS-CoV-2感染后T细胞失调的持续存在突出表明，即使在康复期，MM患者也需要密切监测再次感染情况。CD8+T细胞上的PD-1和TIGIT可能是COVID-19-MM患者分层预后的重要预后因素。此外，免疫治疗可能会下调耗竭检查点PD-1和TIGIT的表达，导致T细胞过度激活和严重的COVID-19。
