Baltuch G H, Villemure J G, McCrea E, Antel J P
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Neurosurgery. 1994 Sep;35(3):450-6; discussion 456. doi: 10.1227/00006123-199409000-00013.
Cellular immune effector mechanisms are implicated as potential therapies for malignant gliomas. We have examined the potential for anti-CD3-activated human peripheral blood-derived CD4+ and CD8+ T cells to induce lysis of human glioma cell lines in vitro, the mechanism of action of these cells, and the capacity of the glioma to inhibit the effect. We found that activated CD4+ and CD8+ T cell preparations containing less than 5% natural killer cells could induce significant lysis of the glioma cell line U251, as measured by an 18-hour, but not 5-hour, chromium-51 or lactate dehydrogenase release assay. This effect was not reproduced using recombinant tumor necrosis factor or inhibited with antitumor necrosis factor antibody. Anti-lymphocyte functional antigen-1 and anti-intercellular adhesion molecule antibodies also did not inhibit the effect. Glioma-derived supernatant could inhibit the proliferation of the T cells but not the cytotoxic effect. Human fetal astrocytes were also susceptible to the cytotoxic effect of the activated T cells. These results indicate that activated T cells can induce glioma cytotoxicity via a mechanism independent of tumor necrosis factor. The therapeutic potential of this effector mechanism will depend on its capacity to deliver these cells or their specific effector molecules to the tumor site or to augment the activity of such cells, which accumulate naturally in gliomas.
细胞免疫效应机制被认为是恶性胶质瘤的潜在治疗方法。我们研究了抗CD3激活的人外周血来源的CD4+和CD8+ T细胞在体外诱导人胶质瘤细胞系裂解的潜力、这些细胞的作用机制以及胶质瘤抑制这种效应的能力。我们发现，含有少于5%自然杀伤细胞的活化CD4+和CD8+ T细胞制剂，通过18小时而非5小时的铬-51或乳酸脱氢酶释放试验检测，可诱导胶质瘤细胞系U251发生显著裂解。使用重组肿瘤坏死因子未重现此效应，且抗肿瘤坏死因子抗体也未抑制该效应。抗淋巴细胞功能抗原-1和抗细胞间黏附分子抗体也未抑制该效应。胶质瘤来源的上清液可抑制T细胞增殖，但不抑制细胞毒性作用。人胎儿星形胶质细胞也易受活化T细胞的细胞毒性作用影响。这些结果表明，活化T细胞可通过独立于肿瘤坏死因子的机制诱导胶质瘤细胞毒性。这种效应机制的治疗潜力将取决于其将这些细胞或其特定效应分子递送至肿瘤部位或增强此类细胞活性的能力，此类细胞可自然积聚在胶质瘤中。
