Romani L, Grohmann U, Puccetti P, Nardelli B, Mage M G, Fioretti M C
Institute of Pharmacology, University of Perugia, Italy.
Cell Immunol. 1988 Feb;111(2):365-78. doi: 10.1016/0008-8749(88)90100-1.
To determine whether antigen-presenting ability might be involved in the superior immunogenicity of chemically xenogenized tumors over that of parental cells, we tested a murine lymphoma line xenogenized by a triazene derivative for expression of Ia antigens, ability to present soluble antigen in vitro, and production of factor(s) active in a mouse thymocyte assay. Results showed that Ia antigens, absent on nonimmunogenic parental L5178Y cells, were expressed on a xenogenized, highly immunogenic tumor variant (clone D), as detected by immunofluorescence. While the ability of parental cells to stimulate lymphocyte proliferation in vitro was lost on removal of Ia+ cells from the responder population, considerable augmentation of reactivity was observed upon depletion of Ia+ cells from the population of splenocytes responding to the xenogenized cells. Under these conditions, stimulation was blocked by anti-Ia antibodies, or an anti-L3T4 reagent or antibodies to the novel antigenic determinants induced by xenogenization. In addition, no stimulating activity was observed following exposure of clone D cells to glutaraldehyde or lysosomotropic agents such as chloroquine and ammonia. When the ability of clone D cells to present ovalbumin in vitro was assayed, it was found that the xenogenized cells could present the soluble antigen to specifically primed lymphocytes. Moreover, clone D cells could substitute for splenic adherent cells in the proliferative reaction of splenocytes to concanavalin A. Finally, when the supernate from clone D-cell culture pulsed with phorbol myristic acetate was tested in a mouse thymocyte assay, considerable IL-1-like activity was disclosed.
为了确定抗原呈递能力是否可能参与化学异种移植肿瘤比亲本细胞具有更强免疫原性的过程，我们检测了一种由三氮烯衍生物异种移植的小鼠淋巴瘤细胞系，检测其Ia抗原的表达、体外呈递可溶性抗原的能力以及在小鼠胸腺细胞检测中有活性的因子的产生。结果显示，通过免疫荧光检测，在无免疫原性的亲本L5178Y细胞上不存在的Ia抗原，在一种异种移植的、高度免疫原性的肿瘤变体（克隆D）上表达。虽然从应答群体中去除Ia+细胞后，亲本细胞在体外刺激淋巴细胞增殖的能力丧失，但在对异种移植细胞作出反应的脾细胞群体中去除Ia+细胞后，观察到反应性有相当大的增强。在这些条件下，刺激被抗Ia抗体、抗L3T4试剂或针对异种移植诱导的新抗原决定簇的抗体所阻断。此外，将克隆D细胞暴露于戊二醛或溶酶体促渗剂如氯喹和氨后，未观察到刺激活性。当检测克隆D细胞在体外呈递卵清蛋白的能力时，发现异种移植细胞可以将可溶性抗原呈递给特异性致敏的淋巴细胞。此外，克隆D细胞可以替代脾黏附细胞参与脾细胞对刀豆球蛋白A的增殖反应。最后，当用佛波醇肉豆蔻酸酯脉冲处理的克隆D细胞培养物的上清液在小鼠胸腺细胞检测中进行检测时，发现有相当大的IL-1样活性。
