Mechanism of calcium ionophore and phorbol ester-induced T-cell activation. Accessory cell requirement for T-cell activation.
We examined the role of monocytes in T-cell activation induced by phorbol myristate acetate (PMA) and calcium ionophore ionomycin. Depletion of monocytes from peripheral blood mononuclear cells (PBMC) was associated with the loss of interleukin-2 (IL-2) production, IL-2 receptor (IL-2R) expression and proliferation, in response to either PMA or ionomycin. Addition of monocytes to highly purified T cells resulted in the complete reconstitution of IL-2 production, IL-2R expression and proliferation by PMA-stimulated lymphocytes. Exogenous IL-2, but not interleukin-1 (IL-1), could reconstitute the T-cell responsiveness. Addition of monocytes to highly purified T cells stimulated with ionomycin resulted in partial reconstitution of IL-2 production, IL-2R expression and proliferation. Similarly, the addition of exogenous IL-2 to ionomycin-stimulated T cells only partially reconstituted the response compared with PBMC. These results suggest that monocyte-T-cell interactions contribute to IL-2 production and IL-2R expression and are crucial events for PMA-induced T-cell proliferation. With ionomycin, monocytes play a role, in part, in inducing IL-2 production, IL-2R expression and proliferation. However, IL-2 is not a sufficient signal to induce T-cell proliferative response to ionomycin, suggesting that an IL-2-independent mechanism may exist in ionomycin-induced T-cell proliferation.
Hashimoto
S
S
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Takahashi
Y
Y
Tomita
Y
Y
Hayama
T
T
Sawada
S
S
Horie
T
T
McCombs
C C
CC
Michalski
J P
JP
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate