Human CD3 gamma delta + activated lymphocytes exhibit killer activity in vitro against autologous leukemic cells.
TCR gamma delta expressing T cell clones are able to exhibit in vitro strong cytolytic activity against cultured tumor cell lines as the myeloid K562 or the Burkitt's lymphoma Daudi cell line. We investigate the possibility of developing TCR gamma delta bearing T cell lines from peripheral blood of 2 leukemic patients in complete remission in order to study their ability to kill autologous leukemic cells. T lymphocyte clones are obtained by limiting dilution of lymphocytes from the blood of patients with an acute lymphoblastic leukemia (ALL). The T cell clones are first selected for their CD8- CD4-phenotype and then for their ability to react with the monoclonal antibody anti-CD3 without presenting reactivity with a monoclonal antibody directed against the TCR alpha beta. Further biochemical studies have indicated that the CD3 associated structure expressed on the cell membrane of these T cell clones is a gamma delta heterodimer. Functional analysis have indicated that these cloned cells are able to kill in a classical cell mediated lysis assay the autologous leukemic cells only when also LAK activity is observed. Thanks to this clonal expansion 10(10) cells/week indefinitely only 1 sample of peripheral blood will be necessary. Would these results be found with other leukemic patients, we propose to use this procedure for a possible application of killer cells for maintenance therapy of leukemia.
Bensussan
A
A
Unité INSERM U93, Hôpital Saint-Louis, Paris, France.
Lagabrielle
J F
JF
Castaigne
S
S
Boisson
N
N
Miclea
J M
JM
Benbunan
M
M
Degos
L
L
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D002460:Cell Line; D002469:Cell Separation; D002999:Clone Cells / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification*; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins