The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

Eur J Immunol. 1997 Nov;27(11):2840-7. doi: 10.1002/eji.1830271115.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line
  • Cell Movement / immunology
  • Central Nervous System / immunology*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Cytokines / biosynthesis*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / genetics
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred Strains
  • Microglia / immunology
  • Microglia / metabolism
  • RNA, Messenger / biosynthesis
  • Th1 Cells / immunology
  • Th1 Cells / metabolism


  • Cytokines
  • RNA, Messenger
  • Interleukin-12