title: Does the frequency and avidity spectrum of the neuroantigen-specific T cells in the blood mirror the autoimmune process in the central nervous system of mice undergoing experimental allergic encephalomyelitis?
abstract: In humans, studies of autoreactive T cells that mediate multiple sclerosis have been largely confined to testing peripheral blood lymphocytes. Little is known how such measurements reflect the disease-mediating autoreactive T cells in the CNS. This information is also not available for murine experimental allergic encephalomyelitis (EAE); the low number of T cells that can be obtained from the blood or the brain of mice prevented such comparisons. We used single-cell resolution IFN-gamma ELISPOT assays to measure the frequencies and functional avidities of myelin basic protein (MBP:87-99)-specific CD4 cells in SJL mice immunized with this peptide. Functional MBP:87-99-specific IFN-gamma-producing cells were present in the CNS during clinical signs of EAE, but not during phases of recovery. In contrast, MBP:87-99-specific T cells persisted in the blood during all stages of the disease, and were also present in mice that did not develop EAE. Therefore, the increased frequency of MBP:87-99-reactive T cells in the blood reliably reflected the primed state, but not the inflammatory activity of these cells in the brain. The functional avidity of the MBP:87-99-reactive T cells was identical in the brain and blood and did not change over 2 mo as the mice progressed from acute to chronic EAE. Therefore, high-affinity T cells did not become selectively enriched in the target organ, and avidity maturation of the MBP:87-99-specific T cell repertoire did not occur in the observation period. The data may help the interpretation of measurements made with peripheral blood lymphocytes of multiple sclerosis patients.
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943, USA.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Hofstetter
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Targoni
authors.forename: Alexey Y
authors.initials: AY
authors.lastname: Karulin
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.forename: Magdalena
authors.initials: M
authors.lastname: Tary-Lehmann
authors.forename: Paul V
authors.initials: PV
authors.lastname: Lehmann
mesh_terms: D000208:Acute Disease; D000818:Animals; D001324:Autoantigens; D015551:Autoimmunity; D002490:Central Nervous System / Q000276:immunology; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
chemical_list: D001324:Autoantigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C115314:myelin basic protein 87-99; D007371:Interferon-gamma