Cytotoxic and noncytotoxic mechanisms involved in the in vitro anti-leukaemia effects of T cell clones established from a chronic myelogenous leukaemia patient during treatment in vivo with interferon alpha.
T cell clones derived from a chronic myelogenous leukaemia (CML) patient during interferon alpha (IFN alpha, Wellferon) biotherapy preferentially lysed autologous rather than allogeneic CML target cells in an apparently MHC-unrestricted fashion, but also lysed bone marrow cells from certain normal donors regardless of whether or not they shared HLA antigens with the patient. Although T cell clones inhibited both CML and normal bone marrow in the colony-forming assay, they blocked proliferation of CML cells more efficiently than bone marrow cells. This inhibitory effect was mediated at least in part by the tumour necrosis factor alpha (TNF alpha) and IFN gamma secreted by the clones. Antisera to these cytokines partially prevented inhibition. Involvement of additional factors is also suggested in blocking CML cell proliferation because this was not 100% inhibited even by a combination of TNF alpha and IFN gamma. In addition, most clones failed strongly to block the proliferation of normal bone marrow cells, which were susceptible to inhibition by these cytokines.
Pawelec
G
G
Second Department of Internal Medicine, University Medical Clinic, Tübingen, Federal Republic of Germany.
Reutter
M
M
Owsianowsky
M
M
Rehbein
A
A
Busch
F W
FW
D001854:Bone Marrow Cells; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000502:physiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma