Chou T, Shu S
J Immunol. 1987 Sep 15;139(6):2103-9.
We have previously demonstrated that following the adoptive transfer of immune cells, the regression of established pulmonary metastases from a weakly immunogenic sarcoma, MCA 105, required the collaboration of two T cell subsets. In this study, we found that the critical role played by L3T4+ immune cells was to provide a helper function since tumor regression proceeded in the absence of L3T4+ immune cells if exogenous interleukin 2 (IL-2) was administered. To extend these observations, we analyzed the events leading to the induction and generation of L3T4+ and Lyt-2+ immune T cells after immunization of mice with viable tumor cells admixed with Corynebacterium parvum. The basic protocol involved immunization, surgical excision of the immunization site on day 7, and challenge with viable tumor cells on day 21. The ability of mice to reject tumor challenge provided a means to evaluate the occurrence of a systemic antitumor immunity. With the use of this experimental protocol, we have found that depletion of T cell subsets in vivo with either L3T4 or Lyt-2 monoclonal antibodies after active immunization abrogated the development of antitumor immunity. Mice immunized and depleted of L3T4+ but not Lyt-2+ T cells were able to reject tumor challenge if exogenous IL-2 was given for 7 days. However, the rejection of tumor challenge required 3 days of additional exogenous IL-2 administration. These results indicate that the induction of Lyt-2+ immune T cells depended on the helper function of L3T4+ T cells via the secretion of IL-2. In the absence of L3T4+ immune lymphocytes, the expression of antitumor immunity by Lyt-2+ immune cells could be facilitated by in vivo administration of exogenous IL-2. The induction of L3T4+ immune T cells, on the other hand, occurred independently of the Lyt-2+ T cell response because the transfer of spleen cells from Lyt-2+ cell-depleted, immunized animals was able to restore antitumor reactivity in L3T4+ cell-depleted, immunized mice. These results demonstrate the intricate cellular interactions leading to the induction as well as the expression of antitumor immunity.
我们之前已经证明，在免疫细胞过继转移后，来自弱免疫原性肉瘤MCA 105的已建立肺转移灶的消退需要两个T细胞亚群的协作。在本研究中，我们发现L3T4 +免疫细胞发挥的关键作用是提供辅助功能，因为如果给予外源性白细胞介素2（IL-2），在没有L3T4 +免疫细胞的情况下肿瘤仍会消退。为了扩展这些观察结果，我们分析了在用活肿瘤细胞与短小棒状杆菌混合免疫小鼠后，导致L3T4 +和Lyt-2 +免疫T细胞诱导和产生的事件。基本方案包括免疫、在第7天手术切除免疫部位以及在第21天用活肿瘤细胞进行攻击。小鼠排斥肿瘤攻击的能力提供了一种评估全身抗肿瘤免疫发生情况的方法。通过使用该实验方案，我们发现主动免疫后用L3T4或Lyt-2单克隆抗体在体内耗尽T细胞亚群会消除抗肿瘤免疫的发展。免疫并耗尽L3T4 +但未耗尽Lyt-2 + T细胞的小鼠，如果给予外源性IL-2 7天，能够排斥肿瘤攻击。然而，排斥肿瘤攻击需要额外给予3天的外源性IL-2。这些结果表明，Lyt-2 +免疫T细胞的诱导依赖于L3T4 + T细胞通过分泌IL-2发挥的辅助功能。在没有L3T4 +免疫淋巴细胞的情况下，体内给予外源性IL-2可以促进Lyt-2 +免疫细胞对抗肿瘤免疫的表达。另一方面，L3T4 +免疫T细胞的诱导独立于Lyt-2 + T细胞反应发生，因为来自Lyt-2 +细胞耗尽的免疫动物的脾细胞转移能够恢复L3T4 +细胞耗尽的免疫小鼠的抗肿瘤反应性。这些结果证明了导致抗肿瘤免疫诱导和表达的复杂细胞相互作用。
