Stewart-Akers A M, Cairns J S, Tweardy D J, McCarthy S A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, PA 15213.
Blood. 1993 May 15;81(10):2671-8.
The treatment of cancer with lymphokine-activated killer (LAK) cells in conjunction with high-dose interleukin-2 (IL-2) has been limited by the toxicity of IL-2 and the narrow range of tumors that respond to therapy. Cytokines that are capable of augmenting lower doses of IL-2 are, therefore, a major focus of research. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF) can augment low-dose IL-2 LAK induction from murine splenocytes. Anti-tumor necrosis factor alpha (anti-TNF alpha) or anti-interferon gamma (anti-IFN gamma) monoclonal antibodies did not inhibit (IL-2 + GM-CSF)-induced LAK generation, indicating that GM-CSF augmentation does not require TNF alpha or IFN gamma activity. Depletion of natural killer cells before culture did not inhibit low-dose IL-2-induced LAK generation or the ability of GM-CSF to augment LAK generation. In contrast, depletion of both CD4+ and CD8+ T cells before culture inhibited the generation of LAK activity. However, depletion of only CD4+ T cells, or only CD8+ T cells, did not inhibit the generation of IL-2 or (IL-2 + GM-CSF) LAK activity. These results suggest that LAK precursors are present in both the CD4+ and CD8+ T-cell populations and suggest that the addition of GM-CSF to low-dose IL-2 may result in the generation of T-derived LAK cells.
用淋巴因子激活的杀伤细胞（LAK）联合大剂量白细胞介素-2（IL-2）治疗癌症，受到IL-2毒性以及对治疗有反应的肿瘤范围狭窄的限制。因此，能够增强低剂量IL-2作用的细胞因子是研究的主要焦点。我们在此报告，粒细胞-巨噬细胞集落刺激因子（GM-CSF）可增强从小鼠脾细胞诱导产生低剂量IL-2的LAK细胞。抗肿瘤坏死因子α（抗TNFα）或抗干扰素γ（抗IFNγ）单克隆抗体不抑制（IL-2 + GM-CSF）诱导的LAK细胞生成，这表明GM-CSF增强作用不需要TNFα或IFNγ的活性。培养前去除自然杀伤细胞不抑制低剂量IL-2诱导的LAK细胞生成或GM-CSF增强LAK细胞生成的能力。相反，培养前同时去除CD4 +和CD8 + T细胞会抑制LAK活性的产生。然而，仅去除CD4 + T细胞或仅去除CD8 + T细胞并不抑制IL-2或（IL-2 + GM-CSF）LAK活性的产生。这些结果表明，LAK前体细胞存在于CD4 +和CD8 + T细胞群体中，并且表明向低剂量IL-2中添加GM-CSF可能会导致产生T细胞来源的LAK细胞。
