Friedman S M, Neyhard N, Chess L
J Immunol. 1978 Feb;120(2):630-7.
This report describes the primary in vitro generation of human CTL that lyse TNP-derivatized autologous cells. Although in the majority of these studies, a direct cytotoxic response to the TNP-modified autologous stimulators was not achieved, in all experiments the addition of either allogeneic cells or soluble antigen triggered the generation of killer cells which destroy TNP-modified, but not unaltered, autologous targets. Fractionation of responder lymphocyte populations demonstrated that the cytotoxic activity was mediated by T cells. Killer cell specificity was tested by assaying for cytotoxicity to a variety of targets, and by blocking the cytolysis of TNP-altered autologous targets with various populations of nonradiolabeled cells. Results indicated that these CTL were cytotoxic for TNP-modified autologous cells but not unaltered autologous or TNP-modified allogeneic targets. The capacity of soluble antigen and alloantigens to facilitate the in vitro generation of altered-self reactive human CTL is not an isolated phenomenon. This "helper" effect has now been observed for the cytotoxic response to chemically modified autologous cells and MHC identical human leukemic blasts. It is possible that in vivo, similar responses to nonspecific antigenic stimuli may play a role in the maintenance of immune surveillance.
本报告描述了体外初次产生可裂解经三硝基苯（TNP）衍生化的自体细胞的人细胞毒性T淋巴细胞（CTL）。尽管在大多数这些研究中，未实现对TNP修饰的自体刺激细胞的直接细胞毒性反应，但在所有实验中，添加同种异体细胞或可溶性抗原均触发了杀伤细胞的产生，这些杀伤细胞可破坏经TNP修饰而非未改变的自体靶细胞。对反应性淋巴细胞群体进行分级分离表明，细胞毒性活性是由T细胞介导的。通过检测对多种靶细胞的细胞毒性，以及用各种非放射性标记细胞群体阻断TNP改变的自体靶细胞的细胞溶解，来测试杀伤细胞的特异性。结果表明，这些CTL对TNP修饰的自体细胞具有细胞毒性，但对未改变的自体细胞或TNP修饰的同种异体靶细胞无细胞毒性。可溶性抗原和同种异体抗原促进体外产生改变自身反应性人CTL的能力并非孤立现象。现在已观察到这种“辅助”效应也存在于对化学修饰的自体细胞和MHC相同的人白血病母细胞的细胞毒性反应中。在体内，对非特异性抗原刺激的类似反应可能在维持免疫监视中发挥作用。
