The Interleukin (IL) 2 Receptor β Chain is Shared by IL-2 and a Cytokine, Provisionally Designated IL-T, That Stimulates T-Cell Proliferation and the Induction of Lymphokine-Activated Killer Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 11; pp. 4940 - 4944
• Main Authors: Bamford, Richard N., Grant, Angus J., Burton, Jack D., Peters, Christian, Kurys, Gloria, Goldman, Carolyn K., Brennan, Jennifer, Roessler, Erich, Waldman, Thomas A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24-05-1994; National Acad Sciences
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - immunology; B lymphocytes; Cell lines; Cytokines; Cytotoxicity, Immunologic; Epidermal cells; Humans; Interleukin-2 - chemistry; Interleukin-2 - immunology; Interleukin-3 - immunology; Interleukins - chemistry; Interleukins - immunology; Killer Cells, Lymphokine-Activated - immunology; Lymphocyte Activation; Mice; Natural killer cells; Receptors; Receptors, Interleukin-2 - chemistry; Receptors, Interleukin-2 - immunology; Signal Transduction; T lymphocytes; T-Lymphocytes - immunology; Transfection; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.11.4940

Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102-conditioned medium or by 3200-fold-purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R α subunit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-β1, an antibody that binds specifically to IL-2R β subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2α but was inhibited by an antibody to IL-2Rβ, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses IL-2Rα and IL-2Rγ, but not IL-2Rβ. Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2Rβ, 32Dβ cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32Dβ proliferation was inhibited by an anti-IL-2Rβ antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2Rβ subunit.