The role of NK cells in transplant tolerance and rejection

NK 细胞在移植耐受和排斥中的作用

• 批准号: 181827904
• 负责人: Privatdozentin Dr. Elke Eggenhofer
• 金额: --
• 依托单位: Klinik und Poliklinik für Chirurgie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/181827904?language=en
• 关键词: role; NK; cells; transplant; tolerance

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.

自然杀伤(NK)细胞在实体器官移植中是关键的，尽管是二分的参与者，因为它们最近被证明是同种异体移植排斥和耐受诱导的关键贡献者。我们以前的研究表明，这种二分性作用可以通过NK细胞细胞因子依赖的激活状态的差异来解释，因为NK细胞一旦被IL-15预激活，就成为同种异体移植急性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细胞在功能上是不同的，不同的NK细胞亚群对细胞因子介导的激活的反应是不同的。在此基础上，我们推测NK细胞可以根据对细胞因子依赖的激活的高反应性和低反应性分为前耐受性和促炎性NK细胞亚群，并正在寻求这一资金来检验这一假说，并进一步了解不同的NK细胞亚群在移植耐受和排斥中所起的作用。由于NK细胞作为效应细胞在移植中的作用尚未得到充分认识，尤其是在移植后的早期阶段，而且目前缺乏调节NK细胞的治疗策略，我们的工作可能对开发新的临床耐受诱导方案产生重要影响。

项目成果

A Color-Coded Reporter Model to Study the Effect of Immunosuppressants on CD8+ T-Cell Memory in Antitumor and Alloimmune Responses

用于研究免疫抑制剂对抗肿瘤和同种免疫反应中 CD8 T 细胞记忆的影响的颜色编码报告模型

• DOI: 10.1097/tp.0b013e318276d358
• 发表时间: 2013
• 期刊: Transplantation Journal
• 作者: Rovira J;Sabet-Baktach M;Eggenhofer E;Lantow M;Koehl GE;Schlitt HJ;Campistol JM;Geissler EK;Kroemer A
• 通讯作者: Kroemer A

Double Deficiency for RORγt and T-bet Drives Th2-Mediated Allograft Rejection in Mice

RORγt 和 T-bet 的双重缺乏导致小鼠中 Th2 介导的同种异体移植排斥

• DOI: 10.4049/jimmunol.1301741
• 发表时间: 2013
• 期刊: The Journal of Immunology
• 作者: Sabet-Baktach M;Eggenhofer E;Rovira J;Renner P;Lantow M;Farkas SA;Malaisé M;Edtinger K;Shaotang Z;Koehl GE;Dahlke MH;Schlitt HJ;Geissler EK;Kroemer A
• 通讯作者: Kroemer A

Unconventional RORγt+ T Cells Drive Hepatic Ischemia Reperfusion Injury

• DOI: 10.4049/jimmunol.1202975
• 发表时间: 2013-07-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Eggenhofer, Elke;Rovira, Jordi;Kroemer, Alexander
• 通讯作者: Kroemer, Alexander

KLRG1+ natural killer cells protect against pulmonary metastatic disease by immunosurveillance

KLRG1自然杀伤细胞通过免疫监视预防肺转移性疾病

• DOI: 10.4161/onci.28328
• 发表时间: 2014
• 期刊: Oncoimmunology
• 影响因子: 7.2
• 作者: Renner P;Rovira J;Klein C;Schlitt HJ;Geissler EK;Kroemer A
• 通讯作者: Kroemer A

CD27low Natural Killer Cells Prolong Allograft Survival in Mice by Controlling Alloreactive CD8+ T Cells in a T-Bet–Dependent Manner

CD27low 自然杀伤细胞通过以 T-Betâ 依赖性方式控制同种异体反应性 CD8 T 细胞来延长小鼠同种异体移植物的存活率

• DOI: 10.1097/tp.0000000000000585
• 发表时间: 2015
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Lantow M;Eggenhofer E;Sabet- Baktach M;Renner P;Rovira J;Koehl GE;Schlitt HJ;Geissler EK;Kroemer A
• 通讯作者: Kroemer A