Immunobiology of allograft rejection in the absence of IFN-γ:: CD8+ effector cells develop independently of CD4+ cells and CD40-CD40 ligand interactions
Immunobiology of allograft rejection in the absence of IFN-γ:: CD8+ effector cells develop independently of CD4+ cells and CD40-CD40 ligand interactions
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DOI：
10.4049/jimmunol.166.5.3248
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发表时间：
2001-03-01
影响因子：
4.4
通讯作者：
Orosz, CG
中科院分区：
文献类型：
--
作者：
Bishop, DK;Wood, SC;Orosz, CG
野生型（WT）和IFN-γ缺陷型（IFN-γ（-/-））C57 BL/6小鼠均能迅速排斥BALB/c心脏同种异体移植物。当耗尽CD8（+）细胞时，WT和IFN-γ（-/-）小鼠均排斥其同种异体移植物，表明这些小鼠具有共同的CD4介导的、CD8非依赖性排斥机制。然而，当CD4（+）细胞耗尽时，WT小鼠接受了它们的同种异体移植物，而IFN-γ（-/-）受体迅速排斥它们。因此，IFN-γ（-/-）小鼠而非WT小鼠产生了不寻常的⑶ S介导的、CD4非依赖性的同种异体移植物排斥机制。IFN-γ（-/-）小鼠中的同种异体移植物排斥与移植物内产生IL-4的细胞、多形核白细胞和嗜酸性粒细胞的积累相关。此外，这种形式的排斥对抗CD40配体（CD40L）mAb治疗具有抗性，这显著延长了WT小鼠的移植物存活。T细胞耗竭研究证实，抗CD40L治疗未能预防IFN-γ（-/-）小鼠中CDS介导的同种异体移植排斥反应。然而，抗CD40L治疗确实防止了IFN-γ（-/-）小鼠中CD4介导的排斥反应，尽管当CD8（+）T细胞重新聚集在外周时移植物最终被排斥。在CD8介导的排斥反应期间发生的IL-4产生和嗜酸性粒细胞流入移植物中显然是附带现象，因为用抗IL-4 mAb治疗阻断了嗜酸性粒细胞的移植物内积聚，但不干扰同种异体移植排斥。这些研究表明，一种新的，CDS介导的同种异体移植排斥反应机制，这是抵抗实验性免疫抑制，可以发展时，LFN-gamma是有限的。对这种机制的理解被其与Th2样免疫事件的关联所混淆，Th2样免疫事件为移植物提供了独特的组织病理学特征，但对于同种异体移植物排斥反应的过程显然是不必要的。
Both wild-type (WT) and IFN-gamma -deficient (IFN-gamma (-/-)) C57BL/6 mice can rapidly reject BALB/c cardiac allografts, When depleted of CD8(+) cells, both WT and LFN-gamma (-/-) mice rejected their allografts, indicating that these mice share a common CD4-mediated, CD8-independent mechanism of rejection. However, when depleted of CD4(+) cells, WT mice accepted their allografts, while IFN-gamma (-/-) recipients rapidly rejected them. Hence, IFN-gamma (-/-), but not WT mice developed an unusual CDS-mediated, CD4-independent, mechanism of allograft rejection, Allograft rejection in IFN-gamma (-/-) mice was associated with intragraft accumulation of IL-4-producing cells, polymorphonuclear leukocytes, and eosinophils. Furthermore, this form of rejection was resistant to treatment with anti-CD40 ligand (CD40L) mAb, which markedly prolonged graft survival in WT mice. T cell depletion studies verified that anti-CD40L treatment failed to prevent CDS-mediated allograft rejection in IFN-gamma (-/-) mice. However, anti-CD40L treatment did prevent CD4-mediated rejection in IFN-gamma (-/-) mice, although grafts were eventually rejected when CD8(+) T cells repopulated the periphery, The IL-4 production and eosinophil influx into the graft that occurred during CD8-mediated rejection were apparently epiphenomenal, since treatment with anti-IL-4 mAb blocked intragraft accumulation of eosinophils, but did not interfere with allograft rejection. These studies demonstrate that a novel, CDS-mediated mechanism of allograft rejection, which is resistant to experimental immunosuppression, can develop when LFN-gamma is Limiting. An understanding of this mechanism is confounded by its association with Th2-like immune events, which contribute unique histopathologic features to the graft but are apparently unnecessary for the process of allograft rejection.