T cell vaccination in multiple sclerosis.
T cell responses to myelin basic protein (MBP) are implicated to play an important role in the pathogenesis of multiple sclerosis (MS). These MBP autoreactive T cells are found to undergo in vivo activation and clonal expansion in patients with MS. They accumulate in the brain compartment and may reside in the brain lesions of patients with MS. As MBP-reactive T cells potentially hold a central position in initiation and perpetuation of the brain inflammation, specific immune therapies designed to deplete them may improve the clinical course of the disease. In this paper, the therapeutic potential of T cell vaccination in the treatment of MS is discussed in context of its immunological and clinical effect. The results of our phase one clinical trial indicate that T cell vaccination with inactivated MBP autoreactive T cells induces specific regulatory T cell network of the host immune system to deplete circulating MBP-reactive T cells in a clonotype-specific fashion. The immunity induced by T cell vaccination is clonotype-specific and long-lasting. Our longitudinal clinical evaluation further suggests a moderate reduction of rate of clinical exacerbation, disability score and the brain lesions (measured by magnetic resonance imaging) in vaccinated patients, as compared to matched controls. Our study should encourage further investigation on the treatment efficacy of T cell vaccination and further improvement for its clinical application.
Zhang
I
I
Dr L Willems Instituut, Diepenbeek, Belgium.
Raus
J
J
D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D001323:Autoantibodies; D004676:Myelin Basic Protein