A novel mechanism of glucocorticoid-induced immune suppression: The inhibition of T cell-mediated terminal maturation of a murine dendritic cell line
A novel mechanism of glucocorticoid-induced immune suppression: The inhibition of T cell-mediated terminal maturation of a murine dendritic cell line
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DOI：
10.1172/jci118759
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发表时间：
1996-07-01
影响因子：
15.9
通讯作者：
Takashima, A
中科院分区：
文献类型：
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作者：
Kitajima, T;Ariizumi, K;Takashima, A
使用小鼠表皮来源的树突状细胞（DC）系XS 52，我们先前已经观察到与T细胞的抗原特异性相互作用刺激它们的“终末成熟”成为完全专业的DC。在这项研究中，我们检测了地塞米松（DEX）对这种T细胞诱导的事件的影响。当在抗原存在下加入到XS 52 DC和KLH特异性Th 1克隆HDK-1的共培养物中时，相对低浓度（10（-9）-10（-7）M）的DEX基本上或完全阻止了代表终末成熟的每种变化，包括（a）分泌相对大量的IL-1 β、IL-6和TNF α;（B）丧失CD 115（集落刺激因子-1受体）表达和对集落刺激因子-1的增殖反应性;和（c）升高的CD 86（B7-2）表达。XS 52细胞在单独暴露于脂多糖时也经历了终末成熟，DEX也有效地抑制了每一种相同的变化，表明DC可以作为DEX的直接靶点。相比之下，DEX抑制HDK-1 T细胞的XS 52 DC刺激的IL-2分泌，但不抑制伴随T细胞活化的其他变化，包括IFN γ和TNF α的分泌以及CD 25、CD 28和CD 44的表达升高。这些结果揭示了糖皮质激素作用的一种新的免疫抑制机制，即DC直接抑制T细胞介导的终末成熟。
Working with the murine epidermal-derived dendritic cell (DC) line XS52, we have observed previously that antigen-specific interaction with T cells stimulates their ''terminal maturation'' into fully professional DC. In this study we examined the impact of dexamethasone (DEX) on this T cell-induced event, When added to cocultures of XS52 DC and the KLH-specific Th1 clone HDK-1 in the presence of antigen, DEX at relatively low concentrations (10(-9)-10(-7) M) prevented substantially or completely each of the changes that typify terminal maturation, including (a) secretion of relatively large amounts of IL-1 beta, IL-6, and TNF alpha; (b) loss of CD115 (colony-stimulating factor-1 receptor) expression and proliferative responsiveness to colony-stimulating factor-1; and (c) elevated expression of CD86 (B7-2). XS52 cells also underwent terminal maturation upon exposure to lipopolysaccharide alone, and DEX also inhibited effectively each of the same changes, indicating that DC can serve as the direct target of DEX. By contrast, DEX inhibited XS52 DC-stimulated IL-2 secretion by HDK-1 T cells, but not other changes that accompany T cell activation, including the secretion of IFN gamma and TNF alpha and the elevated expression of CD25, CD28, and CD44. These results reveal a new immunosuppressive mechanism of glucocorticoid action, that is, direct inhibition of T cell-mediated terminal maturation by DC.