Functional maturation of proteolipid protein(139-151)-specific Th1 cells in the central nervous system in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a widely adopted animal model system for studying human multiple sclerosis that affects the central nervous system (CNS). To understand the underlying pathogenic mechanisms of the autoimmune T cell response, localization, enumeration and characterization of autoreactive T cells are essential. We assessed encephalitogenic proteolipid protein epitope (PLP(139-151))-specific T cells in the periphery and CNS of SJL/J mice using MHC class II I-As multimers during both pre-clinical and clinical phases of PLP-induced EAE in conjunction with T cell function. Our results strongly suggest that PLP(139-151)-specific CD4+ T cells first expand primarily in the CNS-draining cervical lymph nodes and then migrate to the CNS. In the CNS, these PLP-specific CD4+ T cells accumulate, become activated and differentiate into effector cells that produce IFN-gamma in response to the self-peptide.
Mohindru
Mani
M
Department of Microbiology-Immunology and Institute for Neuroscience, Northwestern University Feinberg Medical School, 303 East Chicago Ave, Chicago, IL 60611, USA.
Kang
Bongsu
B
Kim
Byung S
BS
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma