Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Immunol. 2019 Apr 24;10:887. doi: 10.3389/fimmu.2019.00887. eCollection 2019.
TNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) treatment. Frequencies of peripheral T cell subsets and cytokine expression profiles in memory T cells (T) upon PMA/Ionomycine stimulation were determined by flow cytometry. Antigen-specific CD8 T cell immunity was analyzed through stimulating PBMCs with CMV-EBV-Flu (CEF) viral peptide pool and subsequent intracellular IFNγ staining. Both peripheral CD8 and CD4 T cells from GM treated patients had a shift pattern characterized by an enlarged effector T and a reduced central T cell population when compared to GM untreated group. An increase in the frequencies of TNFα, IL-2, and IL-17 CD8 T cells was observed whereas only TNFαCD4 T cells increased in GM treated patients. Moreover, GM treated patients contained more peripheral IFNγ-producing CD8 T cells specific to CEF viral peptides. Together, these results show a distinct T cell subset pattern and enhanced memory T cell immunity upon GM treatment, suggesting an immunoregulatory effect of TNF inhibitor Golimumab on peripheral memory T cell responses.
TNFα 抑制剂以其高临床疗效改变了类风湿关节炎 (RA) 的治疗格局。然而，它们对 T 细胞回忆反应的影响尚未得到充分阐明。我们旨在分析接受 TNFα 抑制剂戈利木单抗（GM）治疗的 RA 患者记忆 T 细胞的免疫特征。通过流式细胞术测定 PMA/离子霉素刺激后外周 T 细胞亚群和记忆 T 细胞（T）中的细胞因子表达谱。通过用 CMV-EBV-Flu（CEF）病毒肽库刺激 PBMC 并随后进行 IFNγ 胞内染色来分析抗原特异性 CD8 T 细胞免疫。与 GM 未治疗组相比，来自 GM 治疗患者的外周 CD8 和 CD4 T 细胞均表现出一种扩大的效应 T 细胞和减少的中央 T 细胞群体的转移模式。观察到 TNFα、IL-2 和 IL-17 CD8 T 细胞的频率增加，而仅 TNFα CD4 T 细胞在 GM 治疗患者中增加。此外，GM 治疗患者含有更多针对 CEF 病毒肽的外周 IFNγ 产生的 CD8 T 细胞。总之，这些结果显示 GM 治疗后 T 细胞亚群模式明显改变，记忆 T 细胞免疫增强，表明 TNF 抑制剂戈利木单抗对外周记忆 T 细胞反应具有免疫调节作用。
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