title: Surges of increased T cell reactivity to an encephalitogenic region of myelin proteolipid protein occur more often in patients with multiple sclerosis than in healthy subjects.
abstract: We have previously shown that patients with multiple sclerosis (MS) have increased T cell responses to the immunodominant region (residues 184-209) of myelin proteolipid protein (PLP). The present study investigated whether this reactivity fluctuates over time and correlates with disease activity. We performed monthly limiting dilution assays for 12-16 mo in four healthy subjects and five patients with relapsing-remitting MS to quantify the frequencies of circulating T cells proliferating in response to PLP(41-58), PLP(184-199), PLP(190-209), myelin basic protein (MBP), MBP(82-100), and tetanus toxoid. Disease activity was monitored by clinical assessment and gadolinium-enhanced magnetic resonance imaging of the brain. There were fluctuations in the frequencies of autoreactive T cells in all subjects. Compared with healthy controls, MS patients had significantly more frequent surges of T cells reactive to the 184-209 region of PLP, but infrequent surges of T cell reactivity to MBP(82-100). There was temporal clustering of the surges of T cell reactivity to MBP(82-100) and MBP, suggesting T cell activation by environmental stimuli. Some clinical relapses were preceded by surges of T cell reactivity to PLP(184-209), and in one patient there was significant correlation between the frequency of T cells reactive to PLP(184-199) and the total number of gadolinium-enhancing magnetic resonance imaging lesions. However, other relapses were not associated with surges of T cell reactivity to the Ags tested. T cells reactive to PLP(184-209) may contribute to the development of some of the CNS lesions in MS.
authors.affiliation: Department of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Pender
authors.forename: P A
authors.initials: PA
authors.lastname: Csurhes
authors.forename: J M
authors.initials: JM
authors.lastname: Greer
authors.forename: P D
authors.initials: PD
authors.lastname: Mowat
authors.forename: R D
authors.initials: RD
authors.lastname: Henderson
authors.forename: K D
authors.initials: KD
authors.lastname: Cameron
authors.forename: D M
authors.initials: DM
authors.lastname: Purdie
authors.forename: P A
authors.initials: PA
authors.lastname: McCombe
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D016056:Immunodominant Epitopes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments