Denizot F, Wilson A, Battye F, Berke G, Shortman K
Proc Natl Acad Sci U S A. 1986 Aug;83(16):6089-92. doi: 10.1073/pnas.83.16.6089.
The response of peritoneal exudate lymphocytes to allogeneic tumor cells was used to determine whether the in vivo generation of cytotoxic T cells (CTL) involved the proliferation of precursor cells. Ten days post-injection, both cytotoxic activity and the formation of conjugates between lymphocytes and target cells were shown to be specific for the immunizing tumor alloantigens and to be effected by Ly-2+ cells. A cell-sorting-based procedure was developed to isolate specific conjugates between red-fluorescence-tagged CTL and blue-fluorescence-tagged tumor target cells. When [3H]thymidine was administered during the response, almost all isolated conjugate-forming CTL were 3H-labeled on autoradiography. Thus, the CTL were clearly products of dividing cells, a result that contradicts published data. Reassessment of a previously studied system, which suggested that CTL were not products of cell division, indicated that in that system many of the conjugate-forming cytotoxic cells studied were Ly-2- and nonspecific, and thus perhaps not T cells. We conclude that the clonal selection model is applicable to at least one in vivo T-cell response.
利用腹膜渗出淋巴细胞对同种异体肿瘤细胞的反应来确定体内细胞毒性T细胞(CTL)的产生是否涉及前体细胞的增殖。注射后10天,细胞毒性活性以及淋巴细胞与靶细胞之间结合物的形成均显示对免疫肿瘤同种异体抗原有特异性,并受Ly-2 +细胞影响。开发了一种基于细胞分选的程序,以分离红色荧光标记的CTL与蓝色荧光标记的肿瘤靶细胞之间的特异性结合物。在反应过程中给予[3H]胸腺嘧啶核苷时,几乎所有分离出的形成结合物的CTL在放射自显影上都被3H标记。因此,CTL显然是分裂细胞的产物,这一结果与已发表的数据相矛盾。对先前研究的系统进行重新评估,该系统表明CTL不是细胞分裂的产物,结果表明在该系统中,许多研究的形成结合物的细胞毒性细胞是Ly-2-且非特异性的,因此可能不是T细胞。我们得出结论,克隆选择模型至少适用于一种体内T细胞反应。