T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-gamma-induced chemokine Mig.
T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-gamma-induced chemokine Mig.
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DOI：
10.5980/jpnjurol.91.218_2
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发表时间：
1999-11
影响因子：
4.4
通讯作者：
Andrew C. Novick;Hiroshi Toma;Robert L. Fairchild;S. Koga;M. B. Auerbach;T. Engeman
中科院分区：
文献类型：
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作者：
Andrew C. Novick;Hiroshi Toma;Robert L. Fairchild;S. Koga;M. B. Auerbach;T. Engeman
缺乏直接证据表明，具有白细胞趋化特性的细胞因子、趋化因子将同种异体抗原诱导的T细胞招募到同种异体移植物中。我们提出的证据表明，单一趋化因子的中和抑制T细胞向II类MHC不同的同种异体小鼠移植物的渗透和急性排斥反应。在急性排斥反应后期，异基因皮肤移植物表达趋化因子干扰素-γ诱导蛋白-10和干扰素-γ诱导的单核细胞因子(Mig)。当C57BL/6受体接受短程Mig抗血清治疗时，II类MHC完全不同的B6.H-2bm12同种异体移植物的存活时间从移植后第14天延长至第55天。这种治疗还可以抑制T细胞和巨噬细胞对移植物的渗透。B6.H-2bm12同种异体移植也不会被干扰素-γ-/-C57BL/6受体排斥。将Mig直接注射到B6.H-2bm12移植物中，可恢复干扰素-γ缺陷受体的T细胞浸润和排斥反应。因此，干扰素-γ缺乏的受者不能排斥II类MHC不同的同种异体移植物是由于移植物内缺乏Mig产生和同种异体抗原诱导的T细胞向移植物募集。这些结果首次表明，趋化因子中和策略在防止T细胞渗入同种异体移植物和消除急性排斥反应方面具有潜在的作用。
Direct evidence that cytokines with chemoattractant properties for leukocytes, chemokines, recruit alloantigen-primed T cells into transplanted allografts has been lacking. We present evidence that neutralization of a single chemokine inhibits T cell infiltration into class II MHC-disparate murine allografts and acute rejection. The chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma (Mig) are expressed in allogeneic skin grafts during the late stages of acute rejection. Survival of class II MHC-disparate B6.H-2bm12 allografts is prolonged from day 14 to day 55 posttransplant when C57BL/6 recipients are given a short course treatment with an antiserum to Mig. This treatment also inhibits T cell and macrophage infiltration into the allografts. B6.H-2bm12 allografts are also not rejected by IFN-gamma-/- C57BL/6 recipients. Injection of Mig directly into B6.H-2bm12 grafts on IFN-gamma-deficient recipients restores T cell infiltration and rejection. Therefore, the inability of IFN-gamma-deficient recipients to reject the class II MHC-disparate allografts is due to the lack of intraallograft Mig production and alloantigen-primed T cell recruitment to the graft. These results indicate for the first time the potential utility of chemokine neutralization strategies in preventing T cell infiltration into allografts and abrogating acute rejection.