Interleukin-1 and B7/CD28 interaction regulate interleukin-6 production by human T cells.
Production of interleukin-6 (IL-6) by the Th2 subset of murine T cells supposedly contributes to regulation of humoral immunity. Little information exists on IL-6 production by human T cells. We examined the requirements for IL-6 production by purified human blood T cells, completely depleted of IL-6-producing monocyte-accessory cells. Immobilized anti-CD3 mAb alone (coated on the culture wells) was unable to induce IL-6 production, although it could induce production of IL-2 and TNF-alpha. Addition of rIL-1 beta as an accessory signal to anti-CD3-stimulated human T cells induced IL-6 mRNA expression and protein secretion, while IL-2, IL-4, GM-CSF, IFN-gamma, or TNF-alpha did not have any effect. In the presence of IL-1 beta, both CD4+ and CD8+ T cells were able to produce IL-6. We also demonstrated that phorbol 12-myristate 13-acetate (PMA) or triggering of the CD28 molecule is an effective helper signal for IL-6 production by anti-CD3-stimulated T cells. Efficient CD28 ligation was done either by anti-CD28 mAb or by binding to its natural ligand B7/BB1, presented on the 3T6 mouse fibroblast cell line coexpressing transfected human Fc gamma RII (CD32) (to immobilize anti-CD3) and B7/BB1. Finally, we found that combinations of IL-1 beta with anti-CD28 mAb or PMA with anti-CD28 mAb were highly synergistic helper signals for IL-6 production. We conclude that IL-6 production by T cells is not induced by T cell receptor triggering alone, but different intracellular signaling pathways activated by IL-1 beta, CD28 ligation, or PMA efficiently coinduce IL-6 production.
Lorré
K
K
Department of Medicine and Pathophysiology, University of Leuven, Belgium.
Kasran
A
A
Van Vaeck
F
F
de Boer
M
M
Ceuppens
J L
JL
D000328:Adult; D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D002460:Cell Line; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D007375:Interleukin-1; D015850:Interleukin-6; D013755:Tetradecanoylphorbol Acetate