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CD8 + T细胞能够排斥胰岛异种移植物。

CD8+ T cells are capable of rejecting pancreatic islet xenografts.

作者信息

Yi S, Feng X, Hawthorne W, Patel A, Walters S, O'Connell P J

机构信息

National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, New South Wales, Australia.

出版信息

Transplantation. 2000 Sep 27;70(6):896-906. doi: 10.1097/00007890-200009270-00007.

DOI:10.1097/00007890-200009270-00007
PMID:11014643
Abstract

BACKGROUND

In this study, the capacity of CD8+ T cells to act as a potential effector mechanism in pancreatic xenograft rejection was examined.

METHODS

The fate of pancreatic islet xenografts was studied in mice deficient in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock-out (CII K/O) mice.

RESULTS

CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathway.

CONCLUSIONS

The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xenografts.

摘要

背景

在本研究中,检测了CD8 + T细胞在胰腺异种移植排斥反应中作为潜在效应机制的能力。

方法

在缺乏MHC II类分子和CD4 + T细胞的小鼠中研究胰岛异种移植的命运。将胎猪胰腺(FPP)或Wistar大鼠胰岛(RI)移植到非糖尿病或链脲佐菌素诱导的糖尿病I - A基因敲除(CII K/O)小鼠中。

结果

CII K/O小鼠能够排斥RI和FPP移植物。与野生型C57BL/6对照相比,RI移植物存活时间未延长。然而,FPP移植物在CII K/O受体中的存活时间比在C57BL/J6小鼠中更长。在CII K/O小鼠中,RI和FPP移植物排斥均为CD8 + T细胞现象,因为抗CD8单克隆抗体延长了移植物存活时间,CII K/O受体的移植物和脾脏中CD8 + T细胞增加,并且细胞介导的细胞毒性是与穿孔素/颗粒酶B系统激活相关的CD8 + T细胞现象。相比之下,在野生型C57BL/6小鼠中,RI和FPP移植物排斥是CD4 + T细胞依赖性现象,抗CD4单克隆抗体可延长移植物存活时间。CD4 + T细胞数量增加,并且细胞介导的细胞毒性是与Fas/FasL裂解途径激活相关的CD4 + T细胞现象。

结论

结果表明,在缺乏CD4 + T细胞的情况下,CD8 + T细胞能够排斥大鼠和猪的胰岛异种移植物。

相似文献

1
CD8+ T cells are capable of rejecting pancreatic islet xenografts.CD8 + T细胞能够排斥胰岛异种移植物。
Transplantation. 2000 Sep 27;70(6):896-906. doi: 10.1097/00007890-200009270-00007.
2
Without CD4 help, CD8 rejection of pig xenografts requires CD28 costimulation but not perforin killing.在没有CD4辅助的情况下,CD8细胞对猪异种移植物的排斥反应需要CD28共刺激,但不需要穿孔素杀伤作用。
J Immunol. 2001 Dec 1;167(11):6279-85. doi: 10.4049/jimmunol.167.11.6279.
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Prolonged survival of fetal pig islet xenografts in mice lacking the capacity for an indirect response.在缺乏间接反应能力的小鼠中,胎猪胰岛异种移植物的长期存活。
Xenotransplantation. 2004 Nov;11(6):525-30. doi: 10.1111/j.1399-3089.2004.00174.x.
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CD4+ T cells initiate pancreatic islet xenograft rejection via an interferon-gamma-dependent recruitment of macrophages and natural killer cells.
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T cell-activated macrophages are capable of both recognition and rejection of pancreatic islet xenografts.T细胞激活的巨噬细胞能够识别并排斥胰岛异种移植物。
J Immunol. 2003 Mar 1;170(5):2750-8. doi: 10.4049/jimmunol.170.5.2750.
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Islet rejection in perforin-deficient mice: the role of perforin and Fas.穿孔素缺陷小鼠的胰岛排斥反应:穿孔素和Fas的作用
Transplantation. 1997 Apr 15;63(7):951-7. doi: 10.1097/00007890-199704150-00008.
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Delayed rejection of fetal pig pancreas in CD4 cell deficient mice was correlated with residual helper activity.CD4细胞缺陷小鼠中胎猪胰腺的延迟排斥与残余辅助活性相关。
Xenotransplantation. 2000 Nov;7(4):267-74. doi: 10.1034/j.1399-3089.2000.00566.x.
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Natural killer T cell facilitated engraftment of rat skin but not islet xenografts in mice.自然杀伤T细胞促进大鼠皮肤而非胰岛异种移植物在小鼠体内的植入。
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Rat pancreatic islet and skin xenograft survival in CD4 and CD8 knockout mice.大鼠胰岛和皮肤异种移植在CD4和CD8基因敲除小鼠中的存活情况。
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Double-negative T cells, activated by xenoantigen, lyse autologous B and T cells using a perforin/granzyme-dependent, Fas-Fas ligand-independent pathway.由异种抗原激活的双阴性T细胞,通过穿孔素/颗粒酶依赖性、Fas-Fas配体非依赖性途径裂解自体B细胞和T细胞。
J Immunol. 2006 Nov 15;177(10):6920-9. doi: 10.4049/jimmunol.177.10.6920.

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