Thymic origin of some natural killer cells: clonal proliferation of human CD3-16+ cells from CD3-4-8- thymocyte precursors requires the presence of H9 leukemic cells.
Purified CD3-4- thymocyte populations were cultured in the presence of interleukin-2 (IL-2) and peripheral blood lymphocytes (PBL) and/or tumor cell lines as a source of irradiated feeder cells. Maximal cell proliferation was obtained in the presence of a mixture of H9 leukemic cells and normal PBL. More importantly, under these culture conditions, 30%-50% of these cells were found to express CD16 surface antigen after 1-2 weeks of culture. Similar proportions of CD16+ cells could be detected in CD3-4- thymocyte populations that had been further depleted of CD16+ cells. Cloning of CD3-4-16- thymocytes under limiting dilution conditions resulted, in the presence of H9 cells, in more than 50% of CD16+ clones (cloning efficiency 3%-8%). Since some of the surface CD3- clones expressed cytoplasmic CD3 antigen, it has been possible to identify four distinct phenotypic groups of clones (CD16+cyCD3+, CD16+cyCD3-, CD16-cyCD3+, CD16-cyCD3-). Independently of their phenotype, all thymus-derived CD3- clones expressed a strong cytolytic activity against natural killer (NK)-sensitive and NK-resistant tumour target cells. In addition, following stimulation with phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (or PHA alone) all clones released interferon-gamma and tumour necrosis factor-alpha, but not IL-2. Taken together, our data provide evidence that cells which share their phenotypic and functional properties with CD3-CD16+ NK cells can be derived from thymic precursors.
Mingari
M C
MC
Istituto di Oncologia Clinica e Sperimentale, Universitá di Genova, Italy.
Poggi
A
A
Bellomo
R
R
Pella
N
N
Moretta
L
L
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000473:pathology*; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology*; D014407:Tumor Cells, Cultured / Q000502:physiology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate