CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis.
Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R- mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis.
Matejuk
Agata
A
Department of Neurology, Oregon Health and Science University, Portland, Oregon.
Hopke
Corwyn
C
Dwyer
Jami
J
Subramanian
Sandhya
S
Jones
Richard E
RE
Bourdette
Dennis N
DN
Vandenbark
Arthur A
AA
Offner
Halina
H
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009103:Multiple Sclerosis / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000502:physiology*; D015854:Up-Regulation
D011948:Receptors, Antigen, T-Cell