Weiss L, Weigensberg M, Morecki S, Bar S, Cobbold S, Waldmann H, Slavin S
Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Cancer Immunol Immunother. 1990;31(4):236-42. doi: 10.1007/BF01789175.
It is now widely accepted that immunocompetent lymphocytes in allogeneic bone marrow grafts exert an antileukemic effect that contributes to the cure of leukemia. Graft vs leukemia (GVL) effects independent of graft vs host disease were investigated in allogeneic bone marrow chimeras tolerant of host and donor alloantigens. The role of Thy1.2, L3T4 and Lyt2 T lymphocytes as effector cells of GVL were investigated in (BALB/c x C57BL/6)F1 mice inoculated with murine B-cell leukemia and subsequently conditioned with total lymphoid irradiation and cyclophosphamide (200 mg/kg). Mice were reconstituted with C57BL/6 bone marrow cells depleted of well-defined T-cell subsets or enriched for stem cells by the soybean agglutination method. Detection of residual tumor cells, an indicator for efficacy of GVL, was carried out by adoptive transfer of peripheral blood or spleen cells obtained from treated chimeras into secondary naive BALB/c recipients at different time intervals following bone marrow transplantation. Treatment of the primary marrow inoculum with monoclonal anti-Thy1.2 or anti-Lyt2 abolished the GVL effects and all secondary BALB/c recipients developed leukemia within 60 days. On the other hand, the treatment with monoclonal anti-L3T4 did not influence the effect of GVL and all treated recipients remained without leukemia. The data suggest that T cells may mediate GVL effects in the absence of graft vs host disease and in circumstances where tolerance to conventional alloantigens is elicited. Effector cells of GVL across the major histocompatibility complex (MHC) in the murine B-cell leukemia tumor model system appear to be Thy1.2+ Lyt2+ L3T4-. Induction of GVL effects by allogeneic cells tolerant of host MHC suggests that these effects may be independent of graft vs host disease.
现在人们广泛接受的观点是，异基因骨髓移植中有免疫活性的淋巴细胞发挥抗白血病作用，有助于治愈白血病。在对宿主和供体同种异体抗原耐受的异基因骨髓嵌合体中，研究了独立于移植物抗宿主病的移植物抗白血病（GVL）效应。在接种了小鼠B细胞白血病、随后接受全身淋巴照射和环磷酰胺（200mg/kg）预处理的（BALB/c×C57BL/6）F1小鼠中，研究了Thy1.2、L3T4和Lyt2 T淋巴细胞作为GVL效应细胞的作用。用大豆凝集法对C57BL/6骨髓细胞进行处理，去除明确的T细胞亚群或富集干细胞，然后将其移植到小鼠体内。通过在骨髓移植后的不同时间间隔，将从处理过的嵌合体中获得的外周血或脾细胞过继转移到二级未致敏的BALB/c受体中，来检测残留肿瘤细胞，这是GVL疗效的一个指标。用单克隆抗Thy1.2或抗Lyt2处理原发性骨髓接种物可消除GVL效应，所有二级BALB/c受体在60天内都会发生白血病。另一方面，用单克隆抗L3T4处理并不影响GVL效应，所有接受治疗的受体都未患白血病。数据表明，在没有移植物抗宿主病且引发对传统同种异体抗原耐受的情况下，T细胞可能介导GVL效应。在小鼠B细胞白血病肿瘤模型系统中，跨越主要组织相容性复合体（MHC）的GVL效应细胞似乎是Thy1.2+Lyt2+L3T4-。宿主MHC耐受的异基因细胞诱导GVL效应表明，这些效应可能独立于移植物抗宿主病。
