IL-2 RECEPTORS--STRUCTURE AND FUNCTION

人类IL-2受体和相关的细胞因子受体系统正在被研究，以阐明正常、肿瘤和免疫缺陷状态下的T细胞免疫反应。在t细胞被抗原激活后，t细胞免疫反应的大小和持续时间取决于产生的IL-2的量、受体表达的水平和每个事件的时间过程。IL-2受体包含三条链，IL-2Ra、IL-2Rb和gc。Leonard博士于1984年克隆了IL-2Ra，他的团队于1986年发现了IL-2Rb，并于1993年报道了gc链突变导致人类x连锁严重联合免疫缺陷（XSCID，具有T-B+NK-表型）。1995年，gc相关激酶Jak3突变导致常染色体隐性SCID与XSCID难以区分；1998年发现T-B+NK+ SCID是由IL7R基因突变引起的。在过去的一年里，该小组报告了在gc敲除小鼠中成功的基因治疗重组缺陷，为小鼠的主要证据奠定了基础，这是人类XSCID基因治疗的一步。有趣的是，这种纠正可能发生在人gc中，这表明人gc能够与小鼠细胞因子和这些小鼠细胞因子的其他受体成分功能性合作。该小组还报道了细胞因子信号传导的负调节因子CIS（细胞因子诱导的含SH2蛋白，也称为CIS1）与IL-2Rb相关并抑制IL-2信号传导，并推进了其对JAB/SOCS1/SSI-1相关蛋白的作用。il -2诱导基因的鉴定工作仍在继续。最后，该小组报道了一种新型I型细胞因子受体蛋白的cDNA克隆，该蛋白被证明是胸腺基质淋巴生成素（TSLP）的受体。有趣的是，像IL-7一样，TSLP来源于基质。其受体由IL-7Ra + TSLPR组成，而IL-7通过IL-7Ra + gc组成的受体进行信号传递。这些发现有助于解释il - 7ra缺陷小鼠（因此缺乏通过IL-7和TSLP的信号传导）比IL-7缺陷小鼠（只有IL-7信号传导缺陷）更大的缺陷。总的来说，这些研究有助于IL-2和相关细胞因子的信号传导。这些发现与免疫缺陷和t细胞生长的控制有关。

The human IL-2 receptor and related cytokine receptor systems are being studied to clarify the T cell immune response in normal, neoplastic, and immunodeficient states. Following T-cell activation by antigen, the magnitude and duration of the T-cell immune response is determined by the amount of IL-2 produced, levels of receptors expressed, and time course of each event. The IL-2 receptor contains three chains, IL-2Ra, IL-2Rb, and gc. Dr. Leonard cloned IL-2Ra in 1984, his group discovered IL-2Rb in 1986, and reported in 1993 that mutation of the gc chain results in X-linked severe combined immunodeficiency (XSCID, which has a T-B+NK- phenotype) in humans; in 1995 that mutations of the gc-associated kinase, Jak3, result in an autosomal recessive form of SCID indistinguishable from XSCID; and in 1998 that T-B+NK+ SCID results from mutations in the IL7R gene. During the past year, the group reported the successful gene-therapeutic reconstitution of the defect in gc-knockout mice, establishing proof of principal in mice as a step towards the human gene therapy for XSCID. Interestingly, the correction could occur with human gc, indicating the ability of human gc to functional cooperate with murine cytokines and the other receptor components of these murine cytokines. The group also reported that a negative regulator of cytokine signaling, CIS (cytokine-inducible SH2 containing protein; also called CIS1) associates with IL-2Rb and inhibits IL-2 signaling and advanced its work on a related protein, denoted JAB/SOCS1/SSI-1. Work on the identification of IL-2-inducible genes continued. Finally, the group reported the cDNA cloning of a novel type I cytokine receptor protein which was demonstrated to be the receptor for thymic stromal lymphopoietin (TSLP). Interestingly, like IL-7, TSLP is derived from stroma. Its receptor consists of the IL-7Ra + TSLPR, whereas IL-7 signals through a receptor comprising IL-7Ra + gc. These findings help to explain the greater defect in IL-7Ra-deficient mice (which thereby lack signaling via IL-7 and TSLP) than in IL-7-deficient mice (in which only IL-7 signaling is defective). Overall, these studies help to aspects of signaling by IL-2 and related cytokines. These findings have relevance to immunodeficiency and the control of T-cell growth.