Following direct CD40 activation, human primary microglial cells produce IL-12 p40 but not bioactive IL-12 p70.
There is accumulating evidence that interleukin 12 (IL-12) is involved in the pathogenesis of multiple sclerosis. In the periphery, this cytokine is produced by antigen-presenting cells (APCs) following interaction with activated T cells. CD40 ligation plays a crucial role in this production. Microglial cells are thought to play a major role in antigen presentation in the central nervous system. In this work, we examined IL-12 production by human primary microglial cells after CD40 ligation. These cells expressed CD40 and MHC class II following interferon-gamma activation. IL-12 p40 mRNA and protein, but not bioactive IL-12 p70, were detected in response to direct CD40 activation. Microglial cells co-cultured with activated allogenic CD4+ T lymphocytes also produced IL-12 p40 but not IL-12 p70. This IL-12 p40 production was inhibited by anti-CD40 ligand. Altogether, these results suggest that CD40-CD40-ligand interaction provides a signal that triggers IL-12 p40 expression. However, other interaction(s) may be required during antigen presentation for bioactive heterodimeric IL-12 p70 to be produced by microglial cells.
de Goër de Herve
M G
MG
Laboratoire Virus, Neurone et Immunité and Laboratoire d'Immunologie, Université Paris XI and CHU de Bicêtre, Bicêtre, France.
Delfraissy
J F
JF
Taoufik
Y
Y
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D015704:CD4 Antigens; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma