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Transferrin Receptor Induction in Mitogen-Stimulated Human T Lymphocytes is Required for DNA Synthesis and Cell Division and is Regulated by Interleukin 2
Leonard M. Neckers and Jeffrey Cossman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 80, No. 11, [Part 1: Biological Sciences] (Jun. 1, 1983), pp. 3494-3498
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/14562
Page Count: 5
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Transferrin is required by many cells for growth. Mitogen-induced T lymphocyte proliferation is dependent on the presence of both interleukin 2 (IL-2; T-cell growth factor) and transferrin, even though resting lymphocytes do not have receptors for either. Exposure to mitogen (phytohemagglutinin) alone is sufficient to induce transient appearance of IL-2 receptors on lymphocytes. Using monoclonal antibodies to the IL-2 receptor and to the transferrin receptor, we examined those signals required for transferrin receptor induction during T lymphocyte proliferation. Our study has revealed that (i) monocytes, or a monocyte substitute such as the phorbol ester tetradecanoyl-phorbol 13-acetate, are required for transferrin receptor expression after mitogen exposure; (ii) the presence of IL-2 receptors is necessary for transferrin receptor induction; (iii) antibody to the IL-2 receptor inhibits thymidine incorporation (DNA synthesis) in lymphocytes, but only if administered before transferrin receptors have appeared; and (iv) antitransferrin receptor antibody inhibits DNA synthesis but has minimal effect on IL-2 receptor expression. Thus, IL-2 receptor induction leads to transferrin receptor induction and subsequent initiation of DNA synthesis. These data indicate that IL-2 stimulates T lymphocyte proliferation, at least in part, by induction of transferrin receptors on these cells.
Proceedings of the National Academy of Sciences of the United States of America © 1983 National Academy of Sciences