Richieri G V, Kleinfeld A M
Division of Membrane Biology, Medical Biology Institute, La Jolla, CA 92037.
J Immunol. 1991 Oct 15;147(8):2809-15.
Conjugation of CTL with their cognate targets elicits a number of early changes within the target cell that are thought to play an important role in the lytic mechanism. We now report that at times earlier than 5 min after conjugation with allospecific CTL, free fatty acids (FFA) are produced in and then secreted from alloantigen-bearing target cells. Using murine CTL clones with different alloantigen specificities, stimulation of FFA production from target cells was found to be Ag specific. FFA production does not appear to be specific for any particular FFA species. Indeed, a wide spectrum of cis unsaturated as well as saturated FFA are produced. FFA production is well correlated with, and specific for, CTL-mediated target cell lysis. Other means of perturbing or lysing target cells, including freeze/thaw disruption, detergent solubilization, or increasing membrane permeabilization with ionomycin, do not stimulate FFA production. In particular, FFA production is not stimulated by treatment with pore-forming granules under conditions that cause more than 90% target cell lysis. These results suggest that FFA production plays an important role in CTL-mediated lysis because stimulation of FFA release specifically requires an event that is CTL induced, occurs very early after conjugation, and is strongly correlated with CTL-mediated lysis.
细胞毒性T淋巴细胞（CTL）与其同源靶细胞的结合会引发靶细胞内一系列早期变化，这些变化被认为在裂解机制中起重要作用。我们现在报告，在与同种异体特异性CTL结合后不到5分钟的时间里，携带同种异体抗原的靶细胞内会产生游离脂肪酸（FFA），然后分泌到细胞外。使用具有不同同种异体抗原特异性的小鼠CTL克隆，发现靶细胞FFA产生的刺激具有抗原特异性。FFA的产生似乎并非针对任何特定的FFA种类。实际上，会产生广泛的顺式不饱和脂肪酸以及饱和脂肪酸。FFA的产生与CTL介导的靶细胞裂解密切相关且具有特异性。其他干扰或裂解靶细胞的方法，包括冻融破坏、去污剂溶解或用离子霉素增加膜通透性，均不会刺激FFA的产生。特别是，在导致超过90%靶细胞裂解的条件下，用成孔颗粒处理不会刺激FFA的产生。这些结果表明，FFA的产生在CTL介导的裂解中起重要作用，因为FFA释放的刺激特别需要一个由CTL诱导的事件，该事件在结合后很早就会发生，并且与CTL介导的裂解密切相关。
