Generation of cytotoxic T lymphocytes from peripheral blood of leukaemic patients.
Peripheral blood mononuclear cells from 13 patients with acute leukaemia were used to establish long-term interleukin-2-dependent cytotoxic T lymphocytes. Cells were grown in RPMI medium containing interleukin-2 (IL-2, 100 U/ml) and 2.5% conditioned medium prepared by activating normal lymphocytes with phytohaemagglutinin. Proliferation of IL-2-dependent CD3-positive lymphocytes was seen in 1 of 2 acute lymphocytic leukaemia cases (ALL), 1 of 4 acute myelogenous leukaemia cases (AML) (M1) and 8 of 8 more differentiated AML. In 2 cases with detectable leukaemic cell markers (1 ALL and 1 AML) passageable cells were developed, that expressed normal T cell phenotypes (namely CD3, CD4 and CD8) at the expense of leukaemic cells. In 1 of 2 cases, long-term IL-2-cultured cells showed specific cytotoxic activity against autologous leukemic cells. The percentage killing against autologous and two allogeneic target cell lines at a 50/1 effector/target (E/T) ratio was 42%, 9% and 19% respectively. Similarly the cytotoxic activity of IL-2 activated from 4 different individuals against conventional tumour targets K562 and Daudi at a ratio of 50/1 was 29%-68% (median = 55%) and 34%-78% (median = 61%) respectively. It was also found that this killing potential of the activated cells was maintained for as long as culture was continued (median 23 days, range 17-75 days). The mechanism(s) of T cell proliferation at the expense of leukaemic blast cells in the case of a minority of leukaemic patients and the possible clinical therapeutic potential of these cells following in vitro IL-2 activation deserve further investigation.
Department of Medical Oncology, Medical College of the Royal London Hospital, UK.
A M
AM
Nouri
E
E
Dorey
C L
CL
Davis
A
A
Rohatiner
T A
TA
Lister
R T
RT
Oliver
D015703:Antigens, CD / Q000032:analysis; D017077:Culture Media, Conditioned; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D007376:Interleukin-2