Requirement for mitogen, T cell-accessory cell contact, and interleukin 1 in the induction of resting T-cell proliferation.
The role of interleukin 1 (IL-1) and accessory cells (AC) in mitogen-driven, resting human peripheral blood T lymphocyte proliferation was examined utilizing highly purified T-cell preparations. Such preparations fail to respond to optimal concentrations of the lectin phytohemagglutin (PHA) or interleukin 2 (IL-2), indicating the functional depletion of monocytes (Mo.) and of activated T cells, respectively. The requirement for Mo. and IL-1 was quantitatively determined by adding known loads of Mo. and of recombinant human IL-1 alpha or beta forms (r-hIL-1, alpha/beta) to T-cell preparations and monitoring the resultant proliferative responses to the mitogens PHA, concanavalin A (Con A), the anti-CD3 monoclonal antibody (mAb) Leu 4, and Sepharose beads-linked Leu 4. Although some mitogens induced IL-2r gene transcription and surface expression in T cells, all mitogens tested failed to drive T cells to proliferate in the absence of Mo. r-h IL-1, as well as Mo.-conditioned media, failed to support the proliferation of mitogen-treated T cells. However, r-h IL-1 significantly amplified the proliferative responses of mitogen-treated T cells when suboptimal loads of Mo. were added. Both r-h IL-1 alpha and beta forms behaved identically in all the aforementioned experiments. The necessity of T cell-Mo. contact for T-cell proliferation was established by demonstrating that T cells separated from Mo. by a semipermeable membrane which allowed free diffusion macromolecules failed to proliferate to the mitogens tested. In contrast to lectins and anti-CD3 mAb phorbol-12-myristate-13-acetate (PMA) induced on its own a modest proliferative response which was greatly enhanced by r-h IL-1 independent of the addition of monocytes. The mechanism of r-h IL-1 action in supporting PMA-primed, T-cell proliferation involved the induction of IL-2 synthesis. We conclude that IL-1 does not substitute for the need for Mo. in supporting mitogen-driven T-cell proliferation. Mitogens, direct accessory-T-cell contact, and IL-1 each act, in this order, to bring about resting T-cell proliferation. The distinct behavior of PMA might relate to its ability to substitute for monocyte contact in promoting the progress of T cells through the cell cycle.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D015846:Monokines; D011506:Proteins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D008934:Mitogens; D015846:Monokines; D011506:Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate