Dendritic cells and differential usage of the MHC class II transactivator promoters in the central nervous system in experimental autoimmune encephalitis.
In the normal central nervous system (CNS) expression of MHC class II is minimal, but has been found to be highly up-regulated on microglia cells in experimental autoimmune encephalitis (EAE). Here we used the EAE model to examine the regulation of expression of the class II transactivator (CIITA), which is required for activation of MHC class II genes. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55. CIITA mRNA form I (specific for dendritic cells) and form IV (IFN-gamma inducible) but not form III (B cell specific) were detected in brain and spinal cord of mice with acute EAE. In unimmunized or mock-immunized mice, none of the three CIITA forms was found to be induced. Dendritic cells (DC) were identified by immunostainings for CD11c in perivascular and meningeal cell infiltrates in EAE spinal cord and brain. Time-course analysis showed (1) the appearance of DC in the CNS shortly before onset of disease, (2) the recruitment of CD11b cells occuring much earlier and (3) the absence of CIITA and MHC class II expression in these CD11b+ cells at preclinical stages.
Suter
T
T
Section of Clinical Immunology, University Hospital Zürich, Switzerland.
Malipiero
U
U
Otten
L
L
Ludewig
B
B
Muelethaler-Mottet
A
A
Mach
B
B
Reith
W
W
Fontana
A
A
D000818:Animals; D001253:Astrocytes / Q000276:immunology; D018845:CD11 Antigens / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005802:Genes, MHC Class II; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation
D018845:CD11 Antigens; D012333:RNA, Messenger