NON T CELL PRODUCED NOVEL T CELL GROWTH FACTORS

基于体外研究，广泛认为IL-2和IL-4，T 细胞产生的TCGFs，在执行中发挥着绝对重要的作用， T细胞介导的现象。 尽管如此， T细胞产生的TCGFs支持克隆增殖， T细胞依赖性反应期间T细胞效应子的活化 体内，例如排斥，尚未建立。 我们认为IL-2 和IL-4不是移植物排斥反应所必需的 “新的”TCGFs也可以支持抗原激活的细胞增殖， T细胞 事实上，我们对IL-2-/-单药和IL-2-/-、IL-4-/-的研究表明， 双基因敲除（DKO）胰岛细胞同种异体移植物接受者表明， 其它TCGF可支持强烈的胰岛同种异体移植排斥。只要 IL-4缺陷小鼠不产生IL-13，我们认为IL-7和IL-15 （而不是T细胞产物）和IL-9是有效的TCGFs， 很可能是这个角色的候选人。 我们检测到了 白细胞介素-7和白细胞介素-15基因在胰岛移植急性排斥反应中的表达 正常和IL-2-/-敲除受体，以及扩增的基因 在几乎所有的人肾移植活检中表达， 急性排斥反应患者，但不是其他常见的移植原因 功能障碍（Strehlau等人，1997年）。 表达的可能性 IL-7、IL-9和IL-15在急性和慢性炎症中可能起重要作用。 同种异体移植物排斥很少受到关注。 了解 这些TCGFs在同种异体移植排斥反应中作用是至关重要的 在设计有效的治疗策略，以促进长期 植入和耐受性。 我们将探讨这些新的TCGFs的作用和治疗 在胰岛细胞和心脏同种异体移植排斥反应中的意义 通过利用IL-2和IL-4缺陷系统， 小鼠以及作为胰岛和心脏同种异体移植物受体的正常小鼠。

Based on in vitro studies, it is widely believed that IL-2 and IL-4, T cell produced TCGFs, play an absolutely essential role in the execution of T cell mediated phenomena. Nonetheless, an exclusive role for these T-cell produced TCGFs in supporting the clonal proliferation and activation of effector of T cells during T cell dependent reactions in vivo, e.g. rejection, has not been established. We believe that IL-2 and IL-4 are not absolutely necessary for graft rejection as other "novel" TCGFs can also support the proliferation of antigen activated T-cells. Indeed, our studies of IL-2-/- single and IL-2-/-, IL-4-/- double gene knockout (DKO) islet cell allograft recipients indicate that other TCGFs can support vigorous islet allograft rejection. Insofar as IL-4 deficient mice do not produce IL-13, we believe that IL-7 and IL-15 (while not T-cell products) and IL-9 are potent TCGFs and are the most likely candidates for this role. We have detected greatly amplified IL-7 and IL-15 gene expression in acutely rejecting islet allografts of normal and IL-2-/- knockout recipients, as well as amplified gene expression in virtually all human renal allograft biopsies obtained from patients with acute rejection, but not other common causes of graft dysfunction (Strehlau et al., 1997). The possibility that expression of IL-7, IL-9 and IL-15 may play an important role in acute and chronic allograft rejection has received little attention. An understanding of the role of these TCGFs in allograft rejection is critically important in designing effective therapeutic strategies to promote long-term engraftment and tolerance. We will explore the role of these novel TCGFs and the therapeutic implications thereof during islet cell and cardiac allograft rejection by utilizing an IL-2 and IL-4-deficient system, the IL-2-/-, IL-4-/- DKO mouse, as well as normal mice as islet and cardiac allograft recipients.