期刊
JOURNAL OF IMMUNOLOGY
卷 165, 期 9, 页码 5322-5331出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.165.9.5322
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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 PLP41-58, PLP184-199, PLP109-209, myelin basic protein (MBP), MBP82-100, and tetanus toroid. 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 MBP82-100. There was temporal clustering of the surges of T cell reactivity to MEP82-100 and MBP, suggesting T cell activation by environmental stimuli, Some clinical relapses were preceded by surges of T cell reactivity to PLP184-209, and in one patient there was significant correlation between the frequency of T cells reactive to PLP184-199 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 PLP184-209 may contribute to the development of some of the CNS lesions in MS.
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