Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation.
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.
Korngold
R
R
Jefferson Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Leighton
C
C
Manser
T
T
D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D016259:Genes, myc; D006086:Graft vs Host Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006087:Graft vs Host Reaction; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007951:Leukemia, Myeloid / Q000628:therapy; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
D016827:CD8 Antigens