Sutton V R, Vaux D L, Trapani J A
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Australia.
J Immunol. 1997 Jun 15;158(12):5783-90.
Two pathways have been implicated in the induction of apoptosis by cytotoxic T cells: the granule exocytosis pathway and a pathway using CD95 (Fas/APO-1). To test whether apoptosis induced by either of these pathways could be blocked by Bcl-2, we exposed bcl-2-transfected cells to CTL derived from normal, perforin-deficient, or CD95 ligand mutant (gld) mice. Although the levels of Bcl-2 expression achieved were able to protect FDC-P1 and Yac-1 transfectants from a variety of apoptotic stimuli, the cells were not protected from cytolysis mediated by CTL from any of these sources, by NK cells, or granules isolated from CTL. However, Bcl-2 expression significantly inhibited apoptosis induced by purified granzyme B and perforin. These results suggest that while Bcl-2 is capable of inhibiting the apoptotic pathway utilized by perforin and granzyme B, other granule components can bypass this block. We conclude that CTL harbor potent killing mechanism(s) in addition to those provided by CD95 ligand or perforin and granzyme B that cannot be overcome by Bcl-2.
细胞毒性T细胞诱导凋亡涉及两条途径：颗粒胞吐途径和使用CD95（Fas/APO-1）的途径。为了检测这两条途径中任何一条所诱导的凋亡是否能被Bcl-2阻断，我们将转染了bcl-2的细胞暴露于源自正常、穿孔素缺陷或CD95配体突变（gld）小鼠的细胞毒性T淋巴细胞（CTL）中。尽管所达到的Bcl-2表达水平能够保护FDC-P1和Yac-1转染细胞免受多种凋亡刺激，但这些细胞不能免受来自这些来源中任何一种的CTL、自然杀伤细胞（NK细胞）或从CTL分离的颗粒所介导的细胞溶解作用。然而，Bcl-2表达显著抑制了由纯化的颗粒酶B和穿孔素诱导的凋亡。这些结果表明，虽然Bcl-2能够抑制穿孔素和颗粒酶B所利用的凋亡途径，但其他颗粒成分可以绕过这种阻断。我们得出结论，除了CD95配体或穿孔素和颗粒酶B所提供的杀伤机制外，CTL还具有Bcl-2无法克服的强大杀伤机制。
