Development of new method for treatment of head and neck tumors using cytotoxic (killer) T lymphocytes

肿瘤特异性移植抗原（TSTA）的检测是肿瘤免疫学研究的重要内容。一般来说，细胞毒性T淋巴细胞（CTL）在肿瘤细胞的主要组织相容性抗原复合体（MHC）的背景下识别TSTA肽。然而，在这种情况下，任何肿瘤都呈现出ctl识别的几种TSTA肽。我们对CTL的特异性进行了近十年的研究，并获得了在一定培养条件下诱导的CTL能够识别刺激细胞的特殊抗原——x染色体连锁基因产物（Xlgp）的结果。将骨髓细胞作为辅助细胞加入到同种异体混合淋巴细胞培养中，诱导的CTL识别刺激细胞的Xlgp和同种异体MHC。这些结果表明，在这种培养条件下，诱导的CTL具有双抗原特异性受体，这两个受体相互识别两种不同的抗原。诱导的CTL通过T细胞受体识别同种MHC，并通过另一种未知受体识别Xlgp。这些CTL的识别受到Xlgp和MHC的限制。这些结果也表明Xlgp抗原与MHC一样是最重要的抗原，因为Xlgp抗原在这些培养条件下可以调节免疫反应。在本研究中，我们试图找到对刺激细胞的Xlgp抗原具有特异性的CTL的最佳培养条件。未来，我们还将研究寻找肿瘤细胞上的TSTA与刺激淋巴细胞上的Xlgp兼容。通过本研究的结果，我们可以找到对刺激淋巴样细胞的Xlgp和MHC具有严格特异性的CTL的最佳培养条件。

It is most important in tumor immunology that the true tumor specific transplantation antigens (TSTA) are detected. In general, cytotoxic T lymphocytes (CTL) recognized the peptide of TSTA in the context of major histocompatibility antigens complex (MHC) of the tumor cells. In this case, however, any tumors presented the several kinds of TSTA peptides recognized by CTLs.We have studied on the specificity of CTL for about ten years, and have obtained the results that the CTL, induced in some culture conditions, recognized the special antigens, X-chromosome linked gene products (Xlgp), of the stimulator cells. When bone marrow cells, as accessory cells, were added in allogeneic mixed lymphocyte cultures, induced CTL recognized the Xlgp as well as allo MHC of the stimulator cells. These results showed that, in this culture condition, induced CTL had dual antigen specific receptors, and these two receptors recognized two distinct antigens each other. The induced CTL recognized allo MHC by T cell receptor, and also allo Xlgp by another unknown receptor. The recognition of these CTL were restricted with allo Xlgp as well as allo MHC.These results also showed that Xlgp antigens were the most important antigens as like as MHC because the Xlgp antigens could regulate the immune responses in these culture conditions.In this study, we try to find the optimal culture conditions to induce the CTL which had the specificity to the Xlgp antigens of the stimulator cells. In future, we will also study to find the TSTA, on the tumor cells, which is compatible with the Xlgp on the stimulator lymphoid cells.As the results in this study, we could find the optimal culture conditions to induce the CTL which had the strict specificity to the Xlgp, as well as MHC, of the stimulator lymphoid cells.