Bowlin T L, McKown B J, Sunkara P S
Cell Immunol. 1987 Mar;105(1):110-7. doi: 10.1016/0008-8749(87)90060-8.
The objective of the present investigation was to evaluate the requirement for increased ornithine decarboxylase (ODC) activity and polyamine biosynthesis in the induction of cytolytic T lymphocytes (CTL). In this regard, we have utilized alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. DFMO treatment completely abrogated Con A-induced NW T-cell ODC activity. Similarly, DFMO treatment reduced putrescine and spermidine biosynthesis 100 and 87% respectively by the end of a 48-hr incubation period. Polyamine depletion reduced the Con A-mediated polyclonal induction of CTL by 52 and 81% at 24 and 48 hr of culture, respectively. The effect of DFMO on CTL induction could be reversed by the addition of exogenous putrescine. These data indicate that the observed effects of DFMO on CTL induction were mediated through inhibition of polyamine biosynthesis. Therefore, increased ODC activity and polyamine biosynthesis are required for optimal CTL induction. Furthermore, polyamine depletion did not impair IL-2 production; however, IL-2-dependent proliferation was reduced. These data are the first to discriminate between the requirement for polyamines with regard to IL-2 responsiveness, rather than IL-2 production, during a primary T-cell mitogenic response.
本研究的目的是评估在细胞毒性T淋巴细胞（CTL）诱导过程中，鸟氨酸脱羧酶（ODC）活性增加和多胺生物合成的需求。在这方面，我们使用了α-二氟甲基鸟氨酸（DFMO），一种ODC的不可逆抑制剂。DFMO处理完全消除了Con A诱导的NW T细胞ODC活性。同样，在48小时孵育期结束时，DFMO处理分别使腐胺和亚精胺的生物合成减少了100%和87%。在培养24小时和48小时时，多胺耗竭分别使Con A介导的CTL多克隆诱导减少了52%和81%。添加外源性腐胺可逆转DFMO对CTL诱导的影响。这些数据表明，观察到的DFMO对CTL诱导的影响是通过抑制多胺生物合成介导的。因此，最佳CTL诱导需要增加ODC活性和多胺生物合成。此外，多胺耗竭并不损害IL-2的产生；然而，依赖IL-2的增殖减少。这些数据首次区分了在原发性T细胞有丝分裂反应期间，多胺对IL-2反应性而非IL-2产生的需求。
