Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Scand J Immunol. 2013 Sep;78(3):275-84. doi: 10.1111/sji.12081.
Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti-TNF therapy-naïve ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4(+) and CD8(+) T cell populations and inhibited secretion of IFN-γ, IL-13, IL-17A, TNF as well as granzyme A. Infliximab also suppressed CD4(+) and CD8(+) T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen-specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3(+) CD4(+) T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab-mediated disease remission in patients with UC.
许多炎症性肠病（IBD）患者正在接受英夫利昔单抗治疗，这是一种针对 TNF 的抗体。然而，英夫利昔单抗的确切作用机制尚不完全清楚。本研究旨在确定英夫利昔单抗对来自抗 TNF 治疗初治溃疡性结肠炎（UC）患者的临床活动期血液 T 细胞的体外作用。外周血单核细胞在存在或不存在英夫利昔单抗的情况下进行多克隆或抗原刺激。通过流式细胞术检测 T 细胞表型，通过 ELISA 测定细胞因子分泌，通过胸苷测定或 CFSE 染料测定细胞增殖。英夫利昔单抗的存在导致 CD4(+)和 CD8(+)T 细胞群中 CD25 的表达减少，并抑制 IFN-γ、IL-13、IL-17A、TNF 以及颗粒酶 A 的分泌。英夫利昔单抗还抑制 CD4(+)和 CD8(+)T 细胞增殖。这些英夫利昔单抗的作用在多克隆和抗原特异性刺激激活的 T 细胞中均有记录。英夫利昔单抗对 T 细胞凋亡和诱导 FOXP3(+)CD4(+)T 调节细胞的影响是不确定的，取决于起源细胞来源和/或刺激方式和强度。总之，英夫利昔单抗能够降低来自临床活动期 UC 患者的 T 细胞体外激活，如 CD25、增殖和细胞因子分泌。这些数据表明，抑制 T 细胞活性可能是英夫利昔单抗介导的 UC 患者疾病缓解的重要因素。
