Halverson D C, Schwartz G N, Carter C, Gress R E, Fowler D H
Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Blood. 1997 Sep 1;90(5):2089-96.
We have previously shown that allospecific murine CD8+ T cells of the Tc1 and Tc2 phenotype could be generated in vitro, and that such functionally defined T-cell subsets mediated a graft-versus-leukemia (GVL) effect with reduced graft-versus-host disease (GVHD). To evaluate whether analogous Tc1 and Tc2 subsets might be generated in humans, CD8+ T cells were allostimulated in the presence of either interleukin-12 (IL-12) and transforming growth factor-beta (TGF-beta) (Tc1 culture) or IL-4 (Tc2 culture). Tc1-type CD8 cells secreted the type I cytokines IL-2 and interferon gamma (IFN-gamma), whereas Tc2-type cells primarily secreted the type II cytokines IL-4, IL-5, and IL-10. Both cytokine-secreting populations effectively lysed tumor targets when stimulated with anti-T-cell receptor (TCR) antibody; allospecificity of Tc1- and Tc2-mediated cytolytic function was demonstrated using bone marrow-derived stimulator cells as targets. In addition, both Tc1 and Tc2 subsets were capable of mediating cytolysis through the fas pathway. We therefore conclude that allospecific human CD8+ T cells of Tc1 and Tc2 phenotype can be generated in vitro, and that these T-cell populations may be important for the mediation and regulation of allogeneic transplantation responses.
我们之前已经表明，Tc1和Tc2表型的同种特异性小鼠CD8⁺ T细胞能够在体外产生，并且这种功能明确的T细胞亚群介导了移植物抗白血病（GVL）效应，同时降低了移植物抗宿主病（GVHD）。为了评估人类是否可能产生类似的Tc1和Tc2亚群，在白细胞介素-12（IL-12）和转化生长因子-β（TGF-β）存在的情况下（Tc1培养）或IL-4（Tc2培养）对CD8⁺ T细胞进行同种异体刺激。Tc1型CD8细胞分泌I型细胞因子IL-2和干扰素γ（IFN-γ），而Tc2型细胞主要分泌II型细胞因子IL-4、IL-5和IL-10。当用抗T细胞受体（TCR）抗体刺激时，这两个分泌细胞因子的群体都能有效地裂解肿瘤靶细胞；使用骨髓来源的刺激细胞作为靶细胞证明了Tc1和Tc2介导的溶细胞功能的同种特异性。此外，Tc1和Tc2亚群都能够通过fas途径介导细胞溶解。因此，我们得出结论，Tc1和Tc2表型的同种特异性人类CD8⁺ T细胞可以在体外产生，并且这些T细胞群体可能对同种异体移植反应的介导和调节很重要。
