Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene

T cells responsive to T-cell receptor (TCR) determinants may regulate patho genic Th1 responses in patients with multiple sclerosis (MS) through interl eukin (IL)-10-dependent bystander suppression. In this study, innate IL10- and interferon (IFN)-gamma -secreting T cells responsive to TCR peptides we re quantified in peripheral blood mononuclear cells of MS patients and heal thy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but l ow IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patie nts had significantly lower IL-10 frequency responses to the TCR peptides b ut normal responses to concanavalin A. Patients undergoing TCR-peptide vacc ination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells w as inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells' These results suggest that MS patients have diminished frequencie s of innate TCR-reactive T cells that may allow oligoclonal expansion of ac tivated autoreactive Th1 effector cells expressing cognate V genes. Publish ed 2001 Wiley-Liss, Inc.(dagger).