Effective stimulation for IL-12 p35 mRNA accumulation and bioactive IL-12 production of antigen-presenting cells interacted with Th cells.
Bioactive IL-12 is composed of two subunits, p35 and p40. In the APC-Th cell interaction, p40 mRNA accumulation in APC was shown to be up-regulated by stimulation with CD40 ligand (CD40L) on Th cells. However, the CD40-CD40L interaction scarcely induced p35 mRNA accumulation in APC. In the present experiments, p35 mRNA accumulation was induced in splenic macrophages/dendritic cells by the interaction with paraformaldehyde-fixed Th1 cells in the presence of Ag, and the p35 mRNA accumulation was abrogated by the inclusion of anti-I-A in cultures to block TCR/MHC class II interaction. The accumulation was also induced by the stimulation with agonistic anti-I-A. These results indicate that the interaction of the MHC class II molecule with TCR evokes an activation signal for p35 mRNA accumulation in APC. Furthermore, the production of bioactive IL-12 in macrophages/dendritic cells stimulated with CD40L was enhanced by the inclusion of agonistic anti-I-A. The p35 mRNA accumulation and IL-12 production of macrophages/dendritic cells induced by stimulation with OVA-specific fixed Th1 clone expressing CD40L were also enhanced by adding OVA in cultures. These results indicate that the p35 mRNA accumulation induced by MHC class II stimulation plays a role in bioactive IL-12 production.
Yamane
H
H
Department of Allergology, Institute of Medical Science, University of Tokyo, Japan.
Kato
T
T
Nariuchi
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand; D016466:CHO Cells; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005404:Fixatives; D005557:Formaldehyde; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*; D007399:Interphase / Q000276:immunology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; D008562:Membrane Glycoproteins; D011108:Polymers; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12; D005557:Formaldehyde; C003043:paraform