Induction of NK-like activity in T cells by IL-2/anti-CD3 is linked to expression of a new antitumour receptor with specificity for acetylated mannose.
The generation of MHC-unrestricted cytotoxicity of highly enriched human CD3+ T cells (95-99%) by treatment with IL-2 and/or anti-CD3 antibodies was studied. T cells obtained by positive immunomagnetic sorting (anti-CD3) developed comparable specific cytotoxicities against K562 and Daudi cells when cultured with IL-2 and anti-CD3 for 96 h (80% of donors; n = 25). This increase of MHC-unrestricted cytotoxicity correlated fairly well with an increased formation of T cell/tumour cell conjugates. Moreover, simultaneous expression of a rhamnogalacturonan-binding receptor on activated T cells could be demonstrated. Rhamnogalacturonan was reported to enhance cytotoxicity of CD56+ NK cells by effector cell/target cell bridging. Untreated CD3+ cells hardly reacted with rhamnogalacturonan and IL-2-activated T cells showed only a moderate enhancement of cytotoxicity in the presence of rhamnogalacturonan. However, when CD3+ T cells had interacted with anti-CD3 antibodies during cell-sorting or during subsequent culturing with IL-2, enhancement in cytotoxicity and increased formation of lytic effector cell/tumour cell conjugates in the presence of rhamnogalacturonan could be readily demonstrated, indicating a bridging effect analogous to CD56+ NK cells. The conjugate formation of activated T cells with tumour cells as well as the additional rhamnogalacturonan-mediated bridging must be based on the expression of receptors with acetyl mannose specificity, since enhancements of MHC-unrestricted T cell cytotoxicity and conjugate formation were inhibited in a dose-dependent manner when acetylated mannose was present in the assays.
Zollner
T M
TM
Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Tuebingen, Germany.
Zhu
H G
HG
Anderer
F A
FA
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D010368:Pectins / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D007074:Immunoglobulin G; D007376:Interleukin-2; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C082603:acetylmannose receptor; C042491:rhamnogalacturonan I; D007371:Interferon-gamma; D010368:Pectins; D015232:Dinoprostone; D007213:Indomethacin