Fazio J, Kalyan S, Wesch D, Kabelitz D
Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Scand J Immunol. 2014 Dec;80(6):381-9. doi: 10.1111/sji.12221.
Human peripheral blood γδ T cells expressing the Vγ9Vδ2 T cell receptor are activated by microbial or endogenous pyrophosphate antigens and indirectly by nitrogen-containing bisphosphonates. Apart from proliferation, such phosphoantigens induce proinflammatory cytokine production including TNF-α and IFN-γ and trigger cytotoxic effector function. Neutrophil granulocytes are known to modulate T cell activation. The neutrophil serine proteases proteinase 3, elastase and cathepsin G have multiple potential targets and promote microbial killing. In this study, we investigated the effect of the three serine proteases on the in vitro proliferation and effector functions of γδ T cells cultured in serum-free medium. All three proteases inhibited the proliferative activity, suppressed the cytokine production and decreased the cytotoxicity of γδ T cells. Further studies indicated that proteolytic cleavage of IL-2 and modulation of butyrophilin 3A1 (CD277) expression might contribute to the overall inhibition.
表达Vγ9Vδ2 T细胞受体的人类外周血γδ T细胞可被微生物或内源性焦磷酸抗原激活，并被含氮双膦酸盐间接激活。除了增殖外，此类磷酸抗原还可诱导包括TNF-α和IFN-γ在内的促炎细胞因子产生，并触发细胞毒性效应功能。已知中性粒细胞可调节T细胞活化。中性粒细胞丝氨酸蛋白酶蛋白酶3、弹性蛋白酶和组织蛋白酶G具有多个潜在靶点，并促进微生物杀伤。在本研究中，我们调查了这三种丝氨酸蛋白酶对在无血清培养基中培养的γδ T细胞的体外增殖和效应功能的影响。所有三种蛋白酶均抑制γδ T细胞的增殖活性，抑制细胞因子产生，并降低其细胞毒性。进一步研究表明，IL-2的蛋白水解切割和嗜乳脂蛋白3A1（CD277）表达的调节可能是总体抑制的原因。
