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首页> 美国卫生研究院文献>other >Defective in vitro IL-2 production in lupus is an early but secondary event paralleling disease activity: Evidence from the murine parent-into-F1 model supports staging of IL-2 defects in human lupus
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Defective in vitro IL-2 production in lupus is an early but secondary event paralleling disease activity: Evidence from the murine parent-into-F1 model supports staging of IL-2 defects in human lupus

机译：狼疮的体外IL-2产生有缺陷是一种早期但次要事件平行疾病活动：来自鼠亲本的证据 - 进入F1模型支持人类狼疮中的IL-2缺陷的分期

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T cell defects are a well described feature of both human and murine lupus however their exact significance is unclear. Evidence from an induced model of lupus, the P → F1 model of chronic lupus-like GVHD demonstrates that a secondary inducible T cell defect in in vitro IL-2 and CTL responses occurs early in the course of lupus-like disease and well in advance of clinical disease. Defective Th cell function was probed using a novel approach categorizing the response to two stimuli:1) the MHC self restricted response, termed self + X; and 2) the allogeneic response. Using this approach, lupus mice exhibited similar in vitro Th cell pattern i.e. and absent S + X response but preserved allogeneic (termed −/+). In contrast, human lupus patients exhibited three possible response patters, +/+, −/+ or −/− with more severe in vitro T cell impairment correlated with more severe disease. Similarly, patients with other T cell mediated conditions i.e. HIV infection or renal allograft recipients, also exhibited more severe in vitro T cell impairment with greater disease activity or greater immunosuppression respectively. The similar Th response patterns in human and murine T cell mediated conditions indicates that the underlying mechanisms involved are not disease specific but instead reflect common immune responses and validate the use of the P → F1 model for future studies of T cell mediated conditions. These results support the use of prospective monitoring of IL-2 responses in lupus patients. Successful adaptation of this approach to the clinical setting could allow not only earlier therapeutic intervention and reduced organ damage but also earlier tapering of pharmacological agents and reduced untoward effects.

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