Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice.
Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice.
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发表时间：
2001-02
影响因子：
4.4
通讯作者：
J. Yamada;B. Ksander;J. Streilein
中科院分区：
文献类型：
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作者：
J. Yamada;B. Ksander;J. Streilein
目的确定直接同种异体反应型细胞毒性T细胞是否被激活并导致C57 BL/6小鼠眼而非BALB/c小鼠眼的原位角膜移植早期急性衰竭。方法取BALB/c和BALB.B小鼠角膜，原位植入C57 BL/6和β 2微球蛋白基因敲除小鼠（CD 8+细胞毒性T细胞缺陷）眼内。移植物的命运进行了临床评估，并测定受体的T淋巴细胞的能力，裂解靶细胞轴承供体主要（MHC）和/或次要组织相容性（次要H）抗原（直接和间接途径，分别）。结果与BALB/c受体相似，具有排斥角膜同种异体移植物的C57 BL/6小鼠获得了供体少量H特异性T细胞。与BALB/c受体不同，C57 BL/6小鼠-排斥者和受体-获得供体MHC特异性T细胞。β-2微球蛋白敲除小鼠表现出与C57 BL/6小鼠难以区分的角膜同种异体移植物排斥反应，包括早期急性排斥反应，但来自β-2微球蛋白敲除角膜同种异体移植物受体的T细胞不显示对供体MHC或次要H同种抗原特异性的细胞毒性T细胞。结论：尽管C57 BL/6小鼠获得了供体MHC特异性细胞毒性T细胞（直接同种异体反应性细胞），但这些细胞和供体次要H特异性细胞毒性T细胞（间接同种异体反应性细胞）在角膜移植排斥反应中均不起任何重要作用，包括在C57 BL/6眼中唯一观察到的早期急性衰竭。
PURPOSE To determine whether cytotoxic T cells of the direct alloreactive type are activated and responsible for early, acute failure of orthotopic corneal allografts observed in eyes of C57BL/6 but not of BALB/c mice. METHODS Corneas from BALB/c and BALB.B mice were placed orthotopically in eyes of C57BL/6 and beta-2 microglobulin knockout mice (deficient in CD8(+) cytotoxic T cells). Graft fates were assessed clinically, and the T lymphocytes of recipients were assayed for the capacity to lyse target cells bearing donor major (MHC) and/or minor histocompatibility (minor H) antigens (direct and indirect pathways, respectively). RESULTS. Similar to BALB/c recipients, C57BL/6 mice with rejected cornea allografts acquired donor minor H-specific T cells. Unlike BALB/c recipients, C57BL/6 mice-both rejectors and acceptors-acquired donor MHC-specific T cells. beta-2 Microglobulin knockout mice showed rejection of corneal allografts in a manner indistinguishable from C57BL/6 mice, including early, acute rejection, yet T cells from beta-2 microglobulin knockout recipients of corneal allografts displayed no cytotoxic T cells specific for either donor MHC or minor H alloantigens. CONCLUSIONS Although C57BL/6 mice acquired donor MHC-specific cytotoxic T cells (direct alloreactive cells), neither these cells nor donor minor H-specific cytotoxic T cells (indirect alloreactive cells) play any essential role in corneal allograft rejection, including the early acute failure uniquely observed in C57BL/6 eyes.