Short-term evolution of autoreactive T cell repertoire in multiple sclerosis

cells reactive to self-antigens are present in the peripheral blood of pati ents with autoimmune diseases as well as in healthy subjects. Although T ce ll-response to the self-myelin antigen myelin basic protein (MBP) has been widely investigated in multiple sclerosis (MS) patients, very little is kno wn about the evolution over time of this response and its correlation with the disease activity. In recent years magnetic resonance imaging (MRI) tech niques have provided new tools for following the inflammatory activity in t he central nervous system (CNS) of MS patients. In the present study the T cell response to MBP was longitudinally investigated in terms of frequency, epitope specificity, and cytokine production profile in four patients with relapsing-remitting MS enrolled in a gadolinium-enhanced MRI serial study. In spite of different profiles of inflammatory activity within the CNS, al l the patients examined showed major changes In their reactivity to MBP dur ing the follow-up period in terms of both frequency and epitope specificity . Episodic expansions of MBP-specific T cell populations were observed in e ach patient, and overall they did not correlate with disease activity. In t hese patients the expansions: 1) occurred in the context of a steady level of disease activity, 2) correlated with a burst of CNS inflammation, 3) fol lowed the appearance of a new active lesion, and 4) were observed even in t he absence of detectable signs of CNS inflammation during the entire follow -up period. These results suggest that the evolution over time of the T cel l response to a self-antigen such as MBP is more complex than previously ex pected. The short-term repertoire dynamics of autoreactive T cells in MS un derscore the importance of longitudinal studies for evaluating autoreactivi ty to myelin antigens and probably to any self-antigen in other autoimmune diseases. (C) 2001 Wiley-Liss, Inc.