Ioannides C G, Fisk B, Tomasovic B, Pandita R, Aggarwal B B, Freedman R S
Department of Gynecology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Immunol Immunother. 1992;35(2):83-91. doi: 10.1007/BF01741854.
We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8+ TAL, the presence of TNF alpha was associated with a selective increase in CD8+ IL-2R+ (Tac+) cells, and subsequent decrease in CD4+ IL-2R+ (Tac+) cells. These results suggest that the observed facilitation of the outgrowth of CD8+ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF alpha in the analysis of signalling in autologous tumor-reactive CTL.
我们最近报道，可从浸润卵巢恶性腹水的淋巴细胞（TAL）中培养出自体肿瘤特异性细胞毒性T淋巴细胞（CTL）系和克隆。在本研究中，我们研究了肿瘤坏死因子α（TNFα）对CD8⁺TAL诱导、扩增、长期增殖及裂解功能的生物学效应。TNFα上调了CD3⁺CD8⁺CD4⁻TAL表面的白细胞介素2受体（IL-2R）α链（Tac抗原），增强了自体肿瘤特异性CTL的增殖，并在长期培养中增强了其裂解功能。此外，在CD8⁺TAL的诱导和扩增阶段，TNFα的存在与CD8⁺IL-2R⁺（Tac⁺）细胞选择性增加以及随后CD4⁺IL-2R⁺（Tac⁺）细胞减少有关。这些结果表明，TAL培养物中观察到的CD8⁺细胞生长促进作用可能至少部分归因于IL-2R的上调，并表明TNFα在分析自体肿瘤反应性CTL中的信号传导方面具有实用性。
