The role of NK cells in transplant tolerance and rejection

自然杀伤（NK）细胞在实体器官移植中是至关重要的，尽管它们是两种类型的细胞，因为它们最近被证明是同种异体移植排斥反应和耐受诱导的关键因素。我们之前的研究表明，这种分化作用可以通过NK细胞细胞因子依赖性激活状态的差异来解释，因为NK细胞一旦被IL-15预激活，就会成为急性同种异体移植排斥反应中的有效效应细胞。更进一步，我们现在有新的数据表明NK细胞在功能上是异质的，不同的NK细胞亚群对细胞因子介导的激活有不同的反应。基于此，我们推测NK细胞可以根据对细胞因子依赖性激活的“高”和“低”反应性分为促耐受和促炎症NK细胞亚群，并正在寻求这笔资金来验证这一假设，并进一步了解不同NK细胞亚群在移植耐受和排斥中的作用。由于NK细胞作为效应细胞在移植中的作用尚未得到充分的解决，特别是在移植后的早期阶段，并且目前缺乏调节NK细胞的治疗策略，因此我们的工作可能对新的临床耐受诱导方案的发展产生重要影响。

Natural killer (NK) cells are crucial albeit dichotomous players in solid organ transplantation, as they have recently been shown to be critical contributors to both allograft rejection and tolerance induction. Our previous studies show that this dichotomous role can be explained by differences in NK cells’ cytokine-dependent activation status, as NK cells, once preactivated by IL-15, become potent effector cells in acute allograft rejection. Going one step further, we now have new data demonstrating that NK cells are functionally heterogeneous and that distinct NK cell subsets respond differently to cytokine-mediated activation. Based on this we speculate that NK cells can be classified into pro-tolerant and pro-inflammatory NK cell subsets according to “high” and “low” responsiveness to cytokine-dependent activation, and are seeking this funding to test this hypothesis and gain further understanding of the role distinct NK cell subsets play in transplant tolerance and rejection. Since the role of NK cells as effector cells in transplantation has not been adequately addressed, especially in the early phase posttransplantation, and therapeutic strategies to modulate NK cells are currently lacking, our work may have an important impact on the development of new clinical tolerance induction protocols.