CYTOTOXIC AND NONCYTOTOXIC MECHANISMS INVOLVED IN THE INVITRO ANTILEUKEMIA EFFECTS OF T-CELL CLONES ESTABLISHED FROM A CHRONIC MYELOGENOUS LEUKEMIA PATIENT DURING TREATMENT INVIVO 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.