Quantitative Proteome Profiling of CNS-Infiltrating Autoreactive CD4+ Cells Reveals Selective Changes during Experimental Autoimmune Encephalomyelitis

• Published in: Journal of proteome research 2014-08, Vol.13 (8), p.3655-3670
• Main Authors: Turvey, Michelle E, Koudelka, Tomas, Comerford, Iain, Greer, Judith M, Carroll, William, Bernard, Claude C. A, Hoffmann, Peter, McColl, Shaun R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion - genetics; Cell Movement - genetics; Central Nervous System - cytology; Central Nervous System - metabolism; Chromatography, High Pressure Liquid; Encephalomyelitis, Autoimmune, Experimental - metabolism; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic - genetics; Mass Spectrometry; Mice; Molecular Sequence Data; Myelin Proteolipid Protein - genetics; Myelin Proteolipid Protein - immunology; Myelin-Oligodendrocyte Glycoprotein - genetics; Peptide Fragments - genetics; Peptide Fragments - immunology; Pertussis Toxin; Proteome - genetics; Proteome - metabolism
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/pr500158r

Experimental autoimmune encephalomyelitis (EAE) is a murine model of multiple sclerosis, a chronic neurodegenerative and inflammatory autoimmune condition of the central nervous system (CNS). Pathology is driven by the infiltration of autoreactive CD4+ lymphocytes into the CNS, where they attack neuronal sheaths causing ascending paralysis. We used an isotope-coded protein labeling approach to investigate the proteome of CD4+ cells isolated from the spinal cord and brain of mice at various stages of EAE progression in two EAE disease models: PLP139–151-induced relapsing-remitting EAE and MOG35–55-induced chronic EAE, which emulate the two forms of human multiple sclerosis. A total of 1120 proteins were quantified across disease onset, peak-disease, and remission phases of disease, and of these 13 up-regulated proteins of interest were identified with functions relating to the regulation of inflammation, leukocyte adhesion and migration, tissue repair, and the regulation of transcription/translation. Proteins implicated in processes such as inflammation (S100A4 and S100A9) and tissue repair (annexin A1), which represent key events during EAE progression, were validated by quantitative PCR. This is the first targeted analysis of autoreactive cells purified from the CNS during EAE, highlighting fundamental CD4+ cell-driven processes that occur during the initiation of relapse and remission stages of disease.