SELECTIVE RADIATION-RESISTANCE OF IMMUNOLOGICALLY INDUCED T-CELLS AS THE BASIS FOR IRRADIATION-INDUCED T-CELL-MEDIATED REGRESSION OF IMMUNOGENIC TUMOR
SELECTIVE RADIATION-RESISTANCE OF IMMUNOLOGICALLY INDUCED T-CELLS AS THE BASIS FOR IRRADIATION-INDUCED T-CELL-MEDIATED REGRESSION OF IMMUNOGENIC TUMOR
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DOI：
10.1002/jlb.49.4.388
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发表时间：
1991-04-01
影响因子：
5.5
通讯作者：
NORTH, RJ
中科院分区：
文献类型：
--
作者：
DUNN, PL;NORTH, RJ
对具有免疫活性但非T细胞缺陷的荷有免疫原性肿瘤的小鼠进行亚致死性全身γ射线照射，可导致T细胞介导的肿瘤完全消退和宿主的长期存活。 辐射的这种显著的T细胞依赖性免疫抑制作用与超过90%的宿主T细胞的破坏和严重的免疫抑制状态相矛盾，这一点可以通过辐射小鼠无法排斥肿瘤同种异体移植物来证明。 此外，尽管暴露于500拉德导致照射前6天植入的同系肿瘤消退，但它导致生长在同一动物上并在1天前植入的不同同系肿瘤的生长增强。 当肿瘤以相反的顺序植入时，也观察到辐射导致6天肿瘤消退但1天肿瘤加速生长的能力。 这意味着，在肿瘤生长的第1天和第6天之间，肿瘤特异性T细胞从放射敏感性状态转化为高度放射抗性状态，几乎可以肯定是因为已经被激活并诱导进入抗肿瘤免疫应答。 效应T细胞的选择性辐射抗性的这种解释是基于出版物，其显示与静息T细胞相比，活化的T细胞具有高度的辐射抗性。 因此，辐射诱导的T细胞介导的肿瘤消退不仅取决于对辐射敏感的抑制性T细胞的破坏，还取决于选择性保留在没有抑制的情况下破坏肿瘤所需的抗辐射激活效应T细胞。
Sublethal, whole-body gamma-irradiation of immunocompetent, but not T cell deficient, mice bearing an established immunogenic tumor results in T-cell-mediated complete tumor regression and in long-term host survival. This striking T-cell-dependent immunotherapeutic action of irradiation was paradoxically associated with the destruction of over 90% of host T cells and with a state of severe immunodepression as evidenced by the inability of irradiated mice to reject a tumor allograft. Furthermore, whereas exposure to 500 rads caused regression of a syngeneic tumor implanted 6 days before irradiation, it caused enhanced growth of a different syngeneic tumor growing on the same animal and implanted 1 day before. This ability of irradiation to cause regression of a 6 day tumor, but accelerated growth of a 1 day tumor, was also seen when the tumors implanted in the reverse order. This means that, between days 1 and 6 of a tumor growth, tumor-specific T cells are converted from a radiosensitive to a highly radioresistant state, almost certainly because of having been activated and inducted into the antitumor immune response. This explanation for the selective radioresistance of effector T cells is based on publications showing that activated, in contrast to resting, T cells are highly radioresistant. Thus irradiation-induced, T-cell-mediated tumor regression depends not only on the destruction of radiosensitive suppressor T cells but also on the selective sparing of radioresistant activated effector T cells that are needed to destroy the tumor in the absence of suppression.