title: A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.
abstract: In early phases of human T-cell lymphotrophic virus I-induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high-affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL-2-specific, we performed a number of studies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine-activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: J D
authors.initials: JD
authors.lastname: Burton
authors.forename: R N
authors.initials: RN
authors.lastname: Bamford
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: A J
authors.initials: AJ
authors.lastname: Grant
authors.forename: G
authors.initials: G
authors.lastname: Kurys
authors.forename: C K
authors.initials: CK
authors.lastname: Goldman
authors.forename: J
authors.initials: J
authors.lastname: Brennan
authors.forename: E
authors.initials: E
authors.lastname: Roessler
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D003470:Culture Media; D004247:DNA; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D007378:Interleukins; D004247:DNA