NON T CELL PRODUCED NOVEL T CELL GROWTH FACTORS

基于体外研究，人们普遍认为IL-2和IL-4，T 细胞产生的TCGF，在执行中起着绝对必要的作用 T细胞介导的现象。尽管如此，这些人的独家角色 T细胞产生TCGF支持克隆性增殖和 T细胞依赖反应中T细胞效应器的激活 活体，例如排斥，还没有确定。我们认为IL-2 和IL-4在移植物排斥反应中不是绝对必要的 “新奇”的TCGF还可以支持抗原激活的增殖 T细胞。事实上，我们对IL-2-/-Single和IL-2-/-，IL-4-/-的研究 双基因敲除(DKO)胰岛细胞同种异体移植受者表明 其他TCGF可以支持强烈的同种异体胰岛移植排斥反应。在以下范围内 IL-4缺陷小鼠不产生IL-13，我们认为IL-7和IL-15 (虽然不是T细胞产物)和IL-9是有效的TCGF，并且是最 可能是这一职位的候选人。我们已经探测到了大大放大的 IL-7和IL-15基因在急性排斥同种异体胰岛移植物中的表达 正常和IL-2-/-敲除受体以及扩增的基因 几乎所有人肾移植活检组织中均有表达 有急性排斥反应的患者，但不是移植的其他常见原因 功能障碍(Strehlau等人，1997年)。这种表达方式的可能性 IL-7、IL-9和IL-15在急慢性疾病中可能起重要作用 同种异体移植排斥反应几乎没有受到关注。一种对 这些TCGF在同种异体移植排斥反应中的作用至关重要。 在设计有效的治疗策略以促进长期 嫁接和宽容。 我们将探索这些新的TCGF的作用和治疗 其在胰岛细胞和心脏移植排斥反应中的意义 通过利用IL-2和IL-4缺乏的系统，IL-2-/-，IL-4-/-DKO 小鼠，以及正常小鼠作为胰岛和心脏同种异体移植受体。

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.