Hamaoka T
Osaka University Medical School.
Gan To Kagaku Ryoho. 1989 Apr;16(4 Pt 2-1):886-96.
Recent studies concerning cellular and molecular mechanisms of T cell-mediated immunity have revealed the involvement of various types of lymphokines. Irrespective of which types of lymphokines and cell-cell interactions among various T cell subsets are involved in the implementation of host immune responses against tumor, the feasible and practical approach is to use both molecular and cellular mechanisms for the augmented induction of effector T cell activity against tumor-resistant antigens (TRA). We have demonstrated previously that the in vivo effector T cells comprise 2 subsets of TRA-specific non-cytolytic CD4- and CD8-positive helper T cells, both of which release lymphokines and activate macrophages as an ultimate anti-tumor cytocidal effector. We have also defined conditions under which enhanced anti-tumor immunity can be obtained by pre-inducing potent helper T cell activity reactive to a certain antigenic determinant such as trinitrophenyl (TNP) residue of muramyl dipeptide (MDP)-derivatives as hapten, and immunized with tumor cells coupled with the corresponding haptenic determinant. This system induced most efficient and physiological cellular and molecular mechanisms responsible for the generation of tumor-specific effector T cell activity in vivo by virtue of the close linkage of hapten-reactive helper T cells and TRA-specific effector-precursor T cells in the microenvironment of hapten-coupled tumor cells. We have subsequently demonstrated that this protocol resulted in enhanced in vivo tumor protective immunity but also was applicable to the immunotherapy whereby a growing solid tumor as well as disseminated leukemia cells could be effectively eradicated in mice. Thus, these results emphasize the role of hapten-reactive helper T cell in augmenting tumor-specific immunity, and this protocol provides an effective maneuver for tumor-specific immunotherapy in human in future.
最近有关T细胞介导免疫的细胞和分子机制的研究揭示了多种淋巴因子的参与。无论在宿主针对肿瘤的免疫反应中涉及何种类型的淋巴因子以及各种T细胞亚群之间的细胞-细胞相互作用，可行且实用的方法是利用分子和细胞机制来增强针对肿瘤抗性抗原（TRA）的效应T细胞活性的诱导。我们先前已经证明，体内效应T细胞包括TRA特异性非细胞溶解性CD4和CD8阳性辅助性T细胞的两个亚群，这两个亚群均释放淋巴因子并激活巨噬细胞作为最终的抗肿瘤杀细胞效应器。我们还确定了通过预先诱导对某些抗原决定簇（如作为半抗原的胞壁酰二肽（MDP）衍生物的三硝基苯基（TNP）残基）有反应的强效辅助性T细胞活性，并与带有相应半抗原决定簇的肿瘤细胞免疫，从而获得增强的抗肿瘤免疫力的条件。该系统通过半抗原反应性辅助性T细胞和TRA特异性效应前体T细胞在半抗原偶联肿瘤细胞微环境中的紧密联系，在体内诱导了最有效和生理性的细胞和分子机制，负责产生肿瘤特异性效应T细胞活性。我们随后证明，该方案不仅增强了体内肿瘤保护性免疫，而且还适用于免疫疗法，从而可以在小鼠中有效根除生长中的实体瘤以及播散性白血病细胞。因此，这些结果强调了半抗原反应性辅助性T细胞在增强肿瘤特异性免疫中的作用，并且该方案为未来人类的肿瘤特异性免疫疗法提供了有效的策略。
