NKG2D及其配体在小鼠心脏同种异体移植中的表达可能在急性排斥反应中起作用。

Expression of NKG2D and its ligand in mouse heart allografts may have a role in acute rejection.

作者信息

Feng L, Ke N, Ye Z, Guo Y, Li S, Li Q, Li Y

机构信息

Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Transplant Proc. 2009 Dec;41(10):4332-9. doi: 10.1016/j.transproceed.2009.08.060.

DOI:10.1016/j.transproceed.2009.08.060

PMID:20005394

Abstract

BACKGROUND

Ligands for the natural killer cell-activating receptor NKG2D, such as retinoic acid early inducible (Rae-1), minor histocompatibility antigen H60 (mouse), and major histocompatibility complex class I chain-related (human) may be expressed by tissues in response to stress. Because NKG2D-ligand engagement may induce natural killer cell activation and provide T-cell costimulation, we examined whether this interaction between innate and adaptive immunity occurred during heart transplant rejection.

METHODS

Hearts from BALB/c mice were heterotopically transplanted into C57BL/6 mice without immunosupression. Grafts were harvested at 1, 3, and 5 days after transplantation. Rae-1, H60, and NKG2D mRNA were analyzed by RT-PCR, and the proteins were detected by immunohistochemistry.

RESULTS

Compared with no expression in naïve BALB/c mice hearts, Rae-1 mRNA levels in heart allografts were detected from days three to five postoperative, H60 on day five, and NKG2D on day three but prominently on day five postoperative. Immunohistochemical assay showed that compared with rare expression in syngeneic cardiac grafts, there were significant protein expressions of Rae-1 and NKG2D in heart allografts from days three to five postoperative and of H60 on day 5 postoperative.

CONCLUSION

This study reported significant mRNA and protein expression of Rae-1, H60, and NKG2D during acute cardiac allograft rejection. The simultaneous and significant expression of NKG2D and its ligands indicated that interactions with innate immunity may promote acute rejection. The results also suggested that Rae-1 and H60 may be new targets to amelioate this immune response.

摘要

背景

自然杀伤细胞激活受体NKG2D的配体，如视黄酸早期诱导基因（Rae-1）、次要组织相容性抗原H60（小鼠）和主要组织相容性复合体I类链相关分子（人类），可由组织在应激反应时表达。由于NKG2D配体的结合可能诱导自然杀伤细胞激活并提供T细胞共刺激，我们研究了这种固有免疫与适应性免疫之间的相互作用是否发生在心脏移植排斥反应过程中。

方法

将BALB/c小鼠的心脏异位移植到未进行免疫抑制的C57BL/6小鼠体内。在移植后1、3和5天采集移植物。通过逆转录聚合酶链反应（RT-PCR）分析Rae-1、H60和NKG2D的信使核糖核酸（mRNA），并通过免疫组织化学检测蛋白质。

结果

与未处理的BALB/c小鼠心脏中无表达相比，心脏同种异体移植物中Rae-1的mRNA水平在术后第3至5天可检测到，H60在第5天，NKG2D在第3天但在术后第5天显著升高。免疫组织化学分析显示，与同基因心脏移植物中罕见表达相比，心脏同种异体移植物中Rae-1和NKG2D的蛋白质表达在术后第3至5天显著增加，H60在术后第5天显著增加。