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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 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.

the journal of immunology/the journal of immunology

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