Effect of FK506 treatment on allocytolytic T lymphocyte induction in vivo: differential effects of FK506 on L3T4+ and Ly2+ T cells.
Effect of FK506 treatment on allocytolytic T lymphocyte induction in vivo: differential effects of FK506 on L3T4+ and Ly2+ T cells.
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FK506 治疗对体内别细胞溶解性 T 淋巴细胞诱导的影响：FK506 对 L3T4 和 Ly2 T 细胞的不同影响。
DOI：
10.1097/00007890-199008000-00021
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发表时间：
1990
期刊：
影响因子：
6.2
通讯作者：
S. Yano
中科院分区：
文献类型：
--
作者：
M. Maruyama;H. Suzuki;N. Yamashita;S. Yano
尽管FK 506已被广泛研究为动物器官移植排斥反应的有效抑制剂，但人们对FK 506对体内同种异体移植T细胞反应的影响知之甚少。在本研究中，我们研究了FK 506对诱导同种异体抗原致敏的小鼠和FK 506处理的同种异体细胞溶解性T淋巴细胞的影响。FK 506可抑制脾细胞和腹腔渗出液细胞（PEC）的CTL诱导，并呈剂量依赖性。时程动力学研究表明，CTL活性明显依赖于FK 506给药的时间。在二次混合淋巴细胞培养（MLC）中，发现这些FK 506给药动物的淋巴细胞在暴露于相同同种异体抗原后重新活化。此外，FK 506对辅助（L3 T4+）和细胞毒性（Ly 2+）T细胞亚群的活化具有不同的影响。同种异体抗原致敏和FK 506处理的小鼠的L3 T4 + T细胞在MLC中产生CTL时具有正常的辅助活性，而这些小鼠的Ly 2 + T细胞在第二次MLC中再次暴露于相同的同种异体抗原时，CTL活性受到严重抑制。在第二次MLC中，外源性IL-2或L3 T4 + T细胞可以克服FK 506对Ly 2 + T细胞诱导CTL的免疫抑制作用。最后，我们已经证明，这种FK 506效应似乎是抗原非特异性的，因为来自同种异体致敏的FK 506处理的小鼠的Ly 2 + T细胞未能诱导针对第三方同种异体抗原的CTL，以及在第二MLC中相同的同种异体抗原。
Although FK506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK506 on T cell responses to allografts in vivo. In the present study, we have studied the effect of FK506 on the induction of allocytolytic T lymphocyte using mice primed with alloantigens and treated with FK506. FK506 suppressed the CTL induction of spleen cells and peritoneal exudate cells (PEC) in a dose-dependent manner. Time-course kinetic studies indicated that the CTL activity was markedly dependent on the time of administration of FK506 to the mice. Lymphocytes from these FK506-treated animals were found to be reactivated upon exposure to the same alloantigens in a secondary mixed lymphocyte culture (MLC). Furthermore, FK506 was shown to have a differential effect on the activation of helper (L3T4+) and cytotoxic (Ly2+) T cell subpopulations. L3T4+ T cells from the mice primed with alloantigens and treated with FK506 had normal helper activity in the generation of CTL in MLC, whereas Ly2+ T cells from these mice were profoundly suppressed CTL activity upon reexposure to the same alloantigens in a secondary MLC. Exogenous IL-2 or L3T4+ T cells could overcome the immunosuppressive effect of FK506 on the CTL induction of Ly2+ T cells in a secondary MLC. Finally, we have demonstrated that this FK506 effect appeared to be antigen nonspecific since Ly2+ T cells from alloprimed FK506-treated mice failed to induce CTL against the third-party alloantigens as well as the same alloantigens in a secondary MLC.