Abstract
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.
Published Version
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