Egawa K, Seo N, Tanino T, Tsukiyama T
Department of Tumor Biology, University of Tokyo, Japan.
Cancer Immunol Immunother. 1995 Dec;41(6):384-8. doi: 10.1007/BF01526558.
Q5 antigens are expressed on the surface of various experimental murine tumor cells. They share partially common antigenicity with Qa-2 alloantigens expressed on normal lymphocytes. For that reason we tested the immunoprotection by anti-Qa-2 immunization of mice against a Q5+ tumor. Nerve fibrosarcoma (NSFA) tumor, which specifically develops metastasis in the lung, has been reported to be poorly immunogenic. However, expression of the Q5 antigen was evident on the surface of NFSA cells. After immunizing (C3H/He x B6.K1)F1 (Qa-2-) mice with B6 (Qa-2+) lymphocytes, the protection against the proliferation of the semi-syngeneic NFSA tumor was examined. First, immunization of normal mice induced resistance to NFSA cell transplants. Second, when the tumor cells were transplanted to the hind foot of a mouse and the resulting tumor was removed by amputating the leg, the mice were protected against the development of lung metastasis after immunization by intraperitoneal inoculation of B6 cells 3 days after tumor removal. Immunization with attenuated NFSA cells in this system failed to protect the mice from lung metastasis. On the other hand, inoculation of the mice with B6 cells without removal of the original tumor on the foot showed little effect on the progression of the tumor. Thus, cytotoxic T lymphocytes (CTL), which seemed to be present in an inactive form in the mice from which the tumor had not been removed, were induced in the mice after the removal of the major tumor followed by immunization with B6 lymphocytes. The induction of CTL by the immunization was suppressed in mice bearing large tumors. Cells stimulated by the tumor antigen seemed to be involved in the suppression. It was also shown that the Q5 antigen is the direct recognition target of the CTL since the activity of Q5-specific CTL clones in lysing tumor cells was inhibited by a monoclonal antibody specific for the Q5 antigen. In contrast to immunization with attenuated tumor cells, our novel allogeneic lymphocyte immunization procedure offers high CTL activation, by-passing the induction of T cell unresponsiveness.
Q5抗原在多种实验性小鼠肿瘤细胞表面表达。它们与正常淋巴细胞上表达的Qa - 2同种异体抗原有部分共同抗原性。因此，我们测试了通过抗Qa - 2免疫小鼠对Q5 +肿瘤的免疫保护作用。神经纤维肉瘤（NSFA）肿瘤特别容易在肺部发生转移，据报道其免疫原性较差。然而，Q5抗原在NFSA细胞表面的表达很明显。在用B6（Qa - 2 +）淋巴细胞免疫（C3H/He×B6.K1）F1（Qa - 2 -）小鼠后，检测了对半同基因NFSA肿瘤增殖的保护作用。首先，正常小鼠的免疫诱导了对NFSA细胞移植的抗性。其次，当将肿瘤细胞移植到小鼠后足并通过截肢去除产生的肿瘤时，在肿瘤切除后3天通过腹腔接种B6细胞进行免疫后，小鼠对肺转移的发生具有抵抗力。在该系统中用减毒的NFSA细胞免疫未能保护小鼠免受肺转移。另一方面，在不切除足部原有肿瘤的情况下给小鼠接种B6细胞对肿瘤进展几乎没有影响。因此，在未切除肿瘤的小鼠中似乎以无活性形式存在的细胞毒性T淋巴细胞（CTL），在切除主要肿瘤后用B6淋巴细胞免疫的小鼠中被诱导产生。在患有大肿瘤的小鼠中，免疫诱导的CTL受到抑制。肿瘤抗原刺激的细胞似乎参与了这种抑制作用。还表明Q5抗原是CTL的直接识别靶标，因为Q5特异性CTL克隆裂解肿瘤细胞的活性被针对Q5抗原的单克隆抗体抑制。与用减毒肿瘤细胞免疫相比，我们新的同种异体淋巴细胞免疫程序提供了高CTL激活，绕过了T细胞无反应性的诱导。
