Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms.
We have reported the establishment of two interleukin (IL)-2-dependent human leukemic cell lines (TALL-103/2 [CD3+TCR gamma delta +] and TALL-104 [CD3+ TCR alpha beta +]) which display major histocompatibility complex nonrestricted tumoricidal activity. Whereas TALL-103/2 cells lyse only natural killer cell-susceptible targets, TALL-104 cells display a broad range of tumor target reactivity. In reverse antibody-dependent cell-mediated cytotoxicity (ADCC), lysis by both cell lines is triggered by monoclonal antibodies (mAb) recognizing CD3 and, to a lesser extent, CD2, but not CD8 or CD56 antigens. In conventional cytotoxic assays, the lytic activity of both cell lines is strictly Ca(2+)-dependent. In reverse ADCC, lysis by TALL-103/2 cells is highly dependent on the presence of Ca2+, whereas TALL-104 cells seem to only partially require extracellular Ca2+. The cytoplasm of both cell lines contains azurophilic granules typical of cytotoxic cells. Northern blot analysis demonstrates mRNA expression of pore-forming protein (PFP; perforin) and serine esterases (SE). The magnitude of expression of these transcripts and of lytic activity depends on the doses of IL-2. Upon deprivation of IL-2, TALL-103/2 cells completely lose cytotoxic granules and function within 16 h, whereas TALL-104 cells progressively lose expression of PFP and SE mRNA, as well as killer activity, within 4 wk. Both anti-CD3 mAb and lysable target cells induce efficient BLT-esterase secretion from TALL-103/2 and TALL-104 cells analogous to findings with conventional cytotoxic T lymphocytes. The stable expression of tumoricidal activity over 2 yr in culture renders these cell lines unique and very useful for studies on the regulation of cell-mediated lysis in vitro and in animal models.
Cesano
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Santoli
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D000920:Antibody-Dependent Cell Cytotoxicity; D002118:Calcium / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000235:genetics; D053804:Granzymes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D004950:Esterases; C022635:serine esterase; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D002118:Calcium