Korngold R, Leighton C, Manser T
Jefferson Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Transplantation. 1994 Aug 15;58(3):278-87.
A model for investigating graft-versus-leukemia (GVL) activity following syngeneic and MHC-compatible allogeneic BMT has been developed in C57BL/6 (B6) mice with use of the c-myc retrovirus-transformed MMB3.19 myeloid leukemia line. The MMB3.19 line was derived from a B6 mouse and expresses monocyte/macrophage markers, including Mac-1, Mac-2, F4/80, and LFA-1, in addition to H-2 class I and class II molecules. A challenge dosage of 10(5) of these leukemia cells was found to be completely lethal when injected into irradiated (850 cGy) B6 recipients, 1 day after the transplantation of syngeneic donor T cell-depleted-bone marrow. The addition of T lymphocytes to the donor inoculum prolonged recipient survival, and both CD4+ and CD8+ subsets were found to be capable of mediating this GVL activity. For the MHC-compatible allogeneic model, the C3H.SW-->B6 (850 cGy) strain combination was utilized, in which CD8+ T cells are known to cause graft-versus-host disease directed to minor histocompatibility antigens expressed by the recipient. In this case, both CD(4+)- and CD(8+)-enriched T cells were found to be capable of mediating GVL activity to MMB3.19 challenge, particularly if donor mice were presensitized with leukemia cells. Of most significance, only the donor CD4+ T cells mediated a GVL effect without the apparent induction of graft-versus-host disease.
利用c-myc逆转录病毒转化的MMB3.19髓系白血病细胞系，在C57BL/6（B6）小鼠中建立了一种用于研究同基因和MHC相容的异基因骨髓移植后移植物抗白血病（GVL）活性的模型。MMB3.19细胞系源自一只B6小鼠，除了H-2 I类和II类分子外，还表达单核细胞/巨噬细胞标志物，包括Mac-1、Mac-2、F4/80和LFA-1。当在同基因供体T细胞去除的骨髓移植后1天，将10(5)个这些白血病细胞的攻击剂量注射到经照射（850 cGy）的B6受体小鼠中时，发现其具有完全致死性。向供体接种物中添加T淋巴细胞可延长受体存活时间，并且发现CD4+和CD8+亚群均能够介导这种GVL活性。对于MHC相容的异基因模型，使用了C3H.SW→B6（850 cGy）品系组合，已知在该组合中CD8+ T细胞会引发针对受体表达的次要组织相容性抗原的移植物抗宿主病。在这种情况下，发现富含CD(4+)和CD(8+)的T细胞均能够介导针对MMB3.19攻击的GVL活性，特别是如果供体小鼠预先用白血病细胞致敏。最显著的是，只有供体CD4+ T细胞介导了GVL效应，而没有明显诱导移植物抗宿主病。
