Cellular and cytokine-mediated effects of CD4-positive lymphocyte lines generated in vitro against chronic myelogenous leukemia.
Leukemia cells from a patient with chronic myelogenous leukemia (CML) in accelerated phase were used to generate CD4+, CD8- T lymphocyte lines from an unrelated normal subject sharing HLA-A2 and DR4 with the patient. In chromium release cytotoxicity assays, lines showed specificity for patient cells and were unreactive against third-party CML and K562 cells. Cytotoxicity was blocked by anti HLA-DR on target cells. Some lines showed preferential cytotoxicity to PHA-induced lymphoblasts and some to CML cells. There was a broad correlation between cytotoxicity to CML cells by 51Cr release and CFU-CM inhibition. However, even weakly cytotoxic lines were inhibitory to CML CFU-GM. This effect was partly mediated by the T cell line supernatant: four of five supernatants tested inhibited the growth of CFU-GM. Antibody neutralization studies demonstrated the presence of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in these supernatants. There was a greater suppression of CML CFU-GM when compared with CFU-GM from normal individuals. One supernatant from a noncytotoxic T cell line stimulated CFU-GM and was demonstrated by antibody neutralization studies to contain interleukin-3 (IL-3) and GM-CSF. These data indicate that alloreacting CD4 cells exert both cytotoxic and cytokine-mediated antileukemia effects which may relate to the graft-vs.-leukemia (GVL) effect in CML following bone marrow transplantation.
Jiang
Y Z
YZ
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Barrett
A J
AJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000276:immunology / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D007377:Interleukin-3 / Q000502:physiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008213:Lymphocyte Activation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D016898:Interferon-alpha; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma