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

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.