The tumor promoter teleocidin induces IL 2 receptor expression and IL 2-independent proliferation of human peripheral blood T cells.
In testing the recently discovered tumor promoter teleocidin (TCD), we found that like phorbol esters, TCD was mitogenic to human peripheral blood lymphocytes (PBL) and preferentially stimulated sheep erythrocyte-rosetted (ER) T cell-enriched populations. Stimulation of PBL with TCD induced synthesis and expression of receptors for interleukin 2 (IL 2), as shown by dot-blot analysis with the use of a synthetic oligonucleotide probe, cell surface staining with anti-Tac antibody followed by fluorescence-activated cell sorter analysis, and a functional proliferation assay in which TCD-stimulated cells were washed free of TCD and were recultured with human recombinant IL 2 (rIL 2). Increased expression of cell surface markers after TCD stimulation of PBL is not general, because TCD did not affect the expression of Leu-2a antigen, and it also reduced the density of Leu-3a and Leu-4 antigens. Stimulation of cultured, IL 2 receptor-positive PBL with rIL 2, but not TCD, was blocked by anti-rIL 2 antibodies. Furthermore, IL 2-specific mRNA was not detected in TCD-stimulated PBL, demonstrating that IL 2 was not required for TCD-induced T cell proliferation. In addition, TCD replaced IL 2 in inducing short-term proliferation of IL 2-dependent murine cytotoxic T cell lines. The findings that TCD induced IL 2-independent proliferation of T cells, and TCD and IL 2 synergized in inducing T cell proliferation, suggest that they initiate T cell proliferation via different mechanisms. The IL 2-independent activation of T cells, and the induction of IL 2 receptor expression by TCD, may be related to its ability to activate protein kinase C in cell membrane.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008235:Lyngbya Toxins / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D002273:Carcinogens; D007376:Interleukin-2; D008235:Lyngbya Toxins; D008934:Mitogens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C022176:teleocidins