T cell vaccination: clinical application in autoimmune diseases

Abstract

 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. We review here the recent application of T cell vaccination in patients with MS to deplete circulating MBP-reactive T cells. The results of our phase I 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 moderately lower rate of clinical exacerbation, disability score, and brain lesions (measured by magnetic resonance imaging) in vaccinated patients than in matched controls. Our study should encourage further investigation on the treatment efficacy of T cell vaccination and further improvement for its clinical administration in other human autoimmune diseases. This review discusses the immune regulation and therapeutic administration of T cell vaccination in human autoimmune diseases, exemplified by our recent T cell vaccination trial in MS.