Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis

• Published in: The Journal of immunology (1950) 2001-04, Vol.166 (8), p.5168-5175
• Main Authors: Juedes, Amy E, Ruddle, Nancy H
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigen Presentation - genetics; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; B7-1 Antigen - biosynthesis; Brain - immunology; Brain - pathology; Cell Line; Cell Movement - immunology; Down-Regulation - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Growth Inhibitors - physiology; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class II - biosynthesis; Lymphocyte Activation; Macromolecular Substances; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia - immunology; Microglia - metabolism; Molecular Sequence Data; Myelin Proteins; Myelin-Associated Glycoprotein - biosynthesis; Myelin-Associated Glycoprotein - immunology; Myelin-Associated Glycoprotein - metabolism; Myelin-Oligodendrocyte Glycoprotein; Nitric Oxide - biosynthesis; Nitric Oxide - physiology; Spinal Cord - immunology; Spinal Cord - pathology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.8.5168

During experimental autoimmune encephalomyelitis (EAE), autoreactive Th1 T cells invade the CNS. Before performing their effector functions in the target organ, T cells must recognize Ag presented by CNS APCs. Here, we investigate the nature and activity of the cells that present Ag within the CNS during myelin oligodendrocyte glycoprotein-induced EAE, with the goal of understanding their role in regulating inflammation. Both infiltrating macrophages (Mac-1(+)CD45(high)) and resident microglia (Mac-1(+)CD45(int)) expressed MHC-II, B7-1, and B7-2. Macrophages and microglia presented exogenous and endogenous CNS Ags to T cell lines and CNS T cells, resulting in IFN-gamma production. In contrast, Mac-1(-) cells were inefficient APCs during EAE. Late in disease, after mice had partially recovered from clinical signs of disease, there was a reduction in Ag-presenting capability that correlated with decreased MHC-II and B7-1 expression. Interestingly, although CNS APCs induced T cell cytokine production, they did not induce proliferation of either T cell lines or CNS T cells. This was attributable to production by CNS cells (mainly by macrophages) of NO. T cell proliferation was restored with an NO inhibitor, or if the APCs were obtained from inducible NO synthase-deficient mice. Thus, CNS APCs, though essential for the initiation of disease, also play a down-regulatory role. The mechanisms by which CNS APCs limit the expansion of autoreactive T cells in the target organ include their production of NO, which inhibits T cell proliferation, and their decline in Ag presentation late in disease.