Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2.
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 tetradecanoylphorbol 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.
D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D014168:Transferrin; D013755:Tetradecanoylphorbol Acetate