Tumor cell lysis by T cells distinct from NK cells and alloantigen-specific cytotoxic T cells.
The generation and mechanism of tumor cell lysis by cytotoxic T cells derived from natural killer cell (NK) and allospecific cytotoxic T cell (CTL)-depleted precursors were examined. NK cells and the precursors of alloantigen-specific CTL were deleted from human peripheral blood lymphocytes by preincubation with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). Following phytohemagglutinin activation, CD3(+), CD4(+) or CD8(+), CD11b(-), CD16(-), and NKH1(-) killer cells capable of lysing a broad spectrum of tumor targets were generated. Cytolysis was not strictly lectin dependent as similar killer cells were generated by activating Leu-Leu-OMe-treated T cells with immobilized monoclonal antibodies to the CD3 molecular complex. The rate of tumor cell lysis by these mitogen-activated T cells was slower than that mediated by CD3(-) NK cells. Tumor cell lysis by mitogen-activated killers was inhibited by anti-CD3 but was not restricted by major histocompatibility complex antigen expression on target cells or by CD4/CD8 expression on effectors. Although similar to NK cells in susceptibility to anti-LFA-1 inhibition of killing, these mitogen-activated killer cells were more sensitive to the inhibitory effects of anti-CD2 than were CD3(-)-activated NK-like cells. Thus, tumor cell lysis by CD3(+) cytotoxic cells generated from Leu-Leu-OMe-treated lymphocytes appears to be mediated in part by mechanisms distinct from those employed by CD3(-) NK cells or antigen-specific CTL.
Thiele
D L
DL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Lipsky
P E
PE
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D004151:Dipeptides; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007519:Isoantigens; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D010641:Phenotype; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D004151:Dipeptides; D000939:Epitopes; D007519:Isoantigens; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; C045139:leucyl-leucine-methyl ester