Induction of IL-12 p40 messenger RNA expression and IL-12 production of macrophages via CD40-CD40 ligand interaction.
The mechanism of IL-12 production has been studied by stimulating macrophages or B cell lines with LPS, Staphylococcus aureus, or phorbol diester. However, since IL-12 plays an important role in the activation of T cells interacting with APC, it is important to study the mechanism of IL-12 production induced by T helper cell-APC interaction. We and others have demonstrated that IL-12 is produced in cultures where Th1 cells are stimulated with Ag or APC. In the present experiments, we studied a role of CD40-CD40 ligand (CD40L) interaction in IL-12 production and obtained the following results: 1) incubation of normal Th1 clone with APC in the presence of Ag induced IL-12 p40 and p35 mRNA accumulation and IL-12 production, and the addition of anti-CD40L blocked the p40 mRNA accumulation and IL-12 production but not p35 mRNA accumulation; 2) when Th1 clone from a CD40L-deficient mouse was used in the incubation, p35 mRNA accumulation was induced, but neither p40 mRNA accumulation nor IL-12 production was induced; 3) CD40L+ Th1 clone, or insect cell membrane expressing mouse CD40L, induced p40 mRNA accumulation and IL-12 production but not p35 mRNA accumulation. These results indicate that the CD40-CD40L interaction plays a critical role in IL-12 p40 mRNA accumulation and bioactive IL-12 production and that p35 mRNA accumulation was regulated via a different mechanism than CD40-CD40L interaction. Most of the cells producing IL-12 were Mac-1+ macrophages.
Kato
T
T
Department of Allergology, Institute of Medical Science, University of Tokyo, Japan.
Hakamada
R
R
Yamane
H
H
Nariuchi
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000961:Antilymphocyte Serum / Q000494:pharmacology; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens / Q000494:pharmacology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D002999:Clone Cells; D005260:Female; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D008024:Ligands; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis*; D013154:Spleen; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000961:Antilymphocyte Serum; D017252:CD3 Complex; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12