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 in creased T cell responses to the immunodominant region (residues 184-209) of myelin proteolipid protein (PLP), The present study investigated whether t his reactivity fluctuates over time and correlates with disease activity,We performed monthly limiting dilution assays for 12-16 mo in four healthy su bjects and five patients with relapsing-remitting MS to quantify the freque ncies 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-enhan ced 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 re active to the 184-209 region of PLP, but infrequent surges of T cell reacti vity to MBP82-100. There was temporal clustering of the surges of T cell re activity to MEP82-100 and MBP, suggesting T cell activation by environmenta l stimuli, Some clinical relapses were preceded by surges of T cell reactiv ity to PLP184-209, and in one patient there was significant correlation bet ween the frequency of T cells reactive to PLP184-199 and the total number o f gadolinium-enhancing magnetic resonance imaging lesions. However, other r elapses were not associated with surges of T cell reactivity to the Ags tes ted. T cells reactive to PLP184-209 may contribute to the development of so me of the CNS lesions in MS.