The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis.
In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE to naive mice. Peptide-specific cells re-isolated from the CNS only produced Th1 cytokines, whereas T cells in the lymph nodes produced both Th1 and Th2 cytokines. Mononuclear cells isolated from the CNS, the majority of which were microglia, presented antigen to and stimulated MBP-specific T cell lines in vitro. Although CNS antigen-presenting cells (APC) supported increased production of interferon (IFN)-gamma mRNA by these T cells, there was no increase in the interleukin (IL)-4 signal, whereas splenic APC induced increases in both IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up-regulated in both infiltrating macrophages and resident microglia from mice with EAE. We have thus shown that a Th1 cytokine bias within the CNS can be induced by CNS APC, and that IL-12 is up-regulated in microglial cells within the CNS of mice with EAE. Microglia may therefore control Th1 cytokine responses within the CNS.
Krakowski
M L
ML
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Canada. michellek@scripps.edu
Owens
T
T
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12