Fowler D H, Breglio J, Nagel G, Hirose C, Gress R E
Transplantation Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA.
Biol Blood Marrow Transplant. 1996 Oct;2(3):118-25.
Donor CD4+ and CD8+ T cells mediate graft-vs.-leukemia (GVL) responses in the allogeneic bone marrow transplantation (alloBMT) setting. To evaluate the role of functional T cell subsets in the mediation of GVL, alloreactive donor CD4+ (Th1/Th2) and CD8+ (Tc1/Tc2) T cells of defined cytokine phenotype were generated by in vitro culture. A leukemia/transplantation model (B6 into B6C3F1; 1050 cGy host irradiation) was established using the bcr/abl-transfected myeloid leukemia line, 32Dp210 (P210; H-2k). Leukemia control mice (1X10(4) P210 cells per recipient) died at day 12.0 post-BMT. Recipients of the CD4+, Th1-type or CD8+, Tc1-type populations were conferred a survival advantage (death at 20.7 and 23.5 days post-BMT, respectively). In contrast, the CD4+, Th2-type population did not mediate GVL (death at 12.3 days). Furthermore, cell mixing experiments demonstrated that the Th2 subset abrogated both Th1- and Tc1-mediated GVL. The CD8+, Tc2 population, which secreted type II cytokines and lysed the P210 leukemia target in vitro, mediated GVL in some experiments; interestingly, the magnitude of Tc2-mediated GVL was inversely related to the level of interleukin-10 (IL-10) secreted in vitro by the Tc2 population. These studies therefore indicate that alloreactive T cells of type I phenotype maximally generate GVL, and that type I/type II interactions are an important consideration for allogeneic transplantation in the setting of leukemic hosts.
在异基因骨髓移植（alloBMT）中，供体CD4⁺和CD8⁺T细胞介导移植物抗白血病（GVL）反应。为了评估功能性T细胞亚群在介导GVL中的作用，通过体外培养产生了具有特定细胞因子表型的同种异体反应性供体CD4⁺（Th1/Th2）和CD8⁺（Tc1/Tc2）T细胞。使用bcr/abl转染的髓系白血病细胞系32Dp210（P210；H-2k）建立了白血病/移植模型（B6小鼠到B6C3F1小鼠；宿主接受1050 cGy照射）。白血病对照小鼠（每个受体接种1×10⁴个P210细胞）在骨髓移植后第12.0天死亡。接受CD4⁺、Th1型或CD8⁺、Tc1型细胞群的受体具有生存优势（分别在骨髓移植后第20.7天和第23.5天死亡）。相比之下，CD4⁺、Th2型细胞群不介导GVL（在第12.3天死亡）。此外，细胞混合实验表明，Th2亚群消除了Th1和Tc1介导的GVL。CD8⁺、Tc2细胞群在体外分泌II型细胞因子并裂解P210白血病靶细胞，在一些实验中介导了GVL；有趣的是，Tc2介导的GVL强度与Tc2细胞群在体外分泌的白细胞介素-10（IL-10）水平呈负相关。因此，这些研究表明，I型表型的同种异体反应性T细胞最大程度地产生GVL，并且I型/II型相互作用是白血病宿主同种异体移植中的一个重要考虑因素。
