The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection
The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection
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DOI：
10.2337/diabetes.51.8.2489
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发表时间：
2002-08-01
期刊：
影响因子：
7.7
通讯作者：
Sayegh, MH
中科院分区：
文献类型：
--
作者：
Abdi, R;Smith, RN;Sayegh, MH
趋化因子是白细胞发育、分化和解剖定位的重要调节因子。CC趋化因子受体5（CCR 5）优先由CD 4（+）T辅助1（Th 1）细胞表达。我们试图在链脲佐菌素诱导的糖尿病小鼠模型中确定CCR 5在胰岛移植排斥反应中的作用。移植的Balb/c胰岛同种异体移植物。移植入CCR 5（-/-）（C57 BL/6）受体的小鼠与移植入野生型对照小鼠的小鼠相比存活时间显著延长（平均存活时间为38 ± 8天）。(10+/-2天; P < 0.0001）。CCR 5（-/-）动物中20%的胰岛同种异体移植物在没有其他治疗的情况下存活>90天。在CCR 5（-/-）小鼠中，移植物内白细胞介素-4和-5的mRNA I表达增加，而干扰素-γ的mRNA I表达降低，对应于T细胞的Th 2模式。与对照中观察到的Th 1模式相比，靶组织中的活化。通过酶联免疫吸附斑点试验，在外周（脾细胞对供体细胞的反应）中也观察到类似的Th 2反应模式I。我们的结论是CCR 5在协调Th 1免疫反应导致胰岛移植排斥反应中起着重要作用。因此，靶向这种趋化因子受体可能提供一种临床上有用的策略，以防止胰岛移植排斥反应。
Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotmin-induced diabetic mouse model. BALB/c islet allografts transplanted. into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice. (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA I expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell. activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern I was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.