Mills C D, North R J
J Exp Med. 1983 May 1;157(5):1448-60. doi: 10.1084/jem.157.5.1448.
The results of this study with the P815 mastocytoma confirm the results of previous studies that showed that the passive transfer of tumor-sensitized T cells from immunized donors can cause the regression of tumors growing in T cell-deficient (TXB) recipients, but not in normal recipients. The key additional finding was that the expression of adoptive immunity against tumors growing in TXB recipients is immediately preceded by a substantial production of cytolytic T cells in the recipients' draining lymph node. On the other hand, failure of adoptive immunity to be expressed against tumors growing in normal recipients was associated with a cytolytic T cell response of much lower magnitude, and a similar low magnitude response was generated in TXB recipients infused with normal spleen cells and in tumor-bearing control mice. Because the passively transferred sensitized T cells possessed no cytolytic activity of their own, the results indicate that the 6-8-d delay before adoptive immunity is expressed represents the time needed for passively transferred helper or memory T cells to give rise to a cytolytic T cell response of sufficient magnitude to destroy the recipient's tumor. In support of this interpretation was the additional finding that inhibition of the expression of adoptive immunity by the passive transfer of suppressor T cells from tumor-bearing donors was associated with a substantially reduced cytolytic T cell response in the recipient's draining lymph node. The results serve to illustrate that interpretation of the results of adoptive immunization experiments requires a knowledge of the events that take place in the adoptively immunized recipient. They support the interpretation that suppressor T cells function in this model to "down-regulate" the production of cytolytic effector T cells.
对P815肥大细胞瘤的这项研究结果证实了先前研究的结果,即来自免疫供体的肿瘤致敏T细胞的被动转移可导致在T细胞缺陷(TXB)受体中生长的肿瘤消退,但在正常受体中则不然。关键的额外发现是,在TXB受体中针对生长肿瘤的过继免疫表达之前,受体引流淋巴结中会大量产生细胞毒性T细胞。另一方面,针对正常受体中生长肿瘤的过继免疫未能表达,与细胞毒性T细胞反应程度低得多有关,并且在注入正常脾细胞的TXB受体和荷瘤对照小鼠中也产生了类似的低程度反应。由于被动转移的致敏T细胞自身不具有细胞溶解活性,结果表明过继免疫表达前6 - 8天的延迟代表了被动转移的辅助性或记忆性T细胞产生足以破坏受体肿瘤的细胞毒性T细胞反应所需的时间。支持这一解释的另一个发现是,来自荷瘤供体的抑制性T细胞的被动转移抑制过继免疫表达,与受体引流淋巴结中细胞毒性T细胞反应大幅降低有关。这些结果表明,对过继免疫实验结果的解释需要了解过继免疫受体中发生的事件。它们支持这样的解释,即抑制性T细胞在该模型中发挥作用以“下调”细胞毒性效应T细胞的产生。