Long-term effects of T cell vaccination in multiple sclerosis
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterised by focal areas of demyelination in the CNS (Ffrench-Constant 1994). Autoimmune processes involving myelin-reactive T cells are considered to play an essential role in the pathogenesis of MS (for a review, see Stinissen et al. 1997). In vivo activated T cells reactive to myelin basic protein (MBP) are clonally expanded in the blood of MS patients and may persist for many years in some patients (Goebels et al. 2000). The activation of MBP-reactive T cells via molecular mimicry could be a common process, as suggested by the high level of cross-reactivity of MBP-reactive T cells to various microbial ligands, even in the absence of any sequence homology (Wucherpfennig et al. 1995,Hemmer et al. 1998). Accidentally stimulated autoreactive T cells however may not automatically lead to autoimmunity. Indeed, several observations support the existence of a peripheral regulatory network that prevents activation or expansion of pathogenic T cells (Cohen et al. 1992). However, an imbalanced regulatory network may lead to sub-optimal suppression of activated pathogenic T cells and give rise to autoimmunity. Administration of attenuated autoreactive T cells as a vaccine (T cell vaccination, TCV) may enhance the regulatory networks to specifically suppress the eliciting autoreactive T cells as shown in experimental autoimmune encephalomyelitis (EAE), an animal model of MS (Ben-Nun et al. 1981,Lider et al. 1988). We have performed a pilot study of TCV with MBP-reactive T cells in a small number of MS patients (Zhang et al. 1993,Medaer et al. 1995). The patients were immunised three times with autologous irradiated MBP-reactive T cell clones (see Figure 1).
KeywordsMultiple Sclerosis Peripheral Blood Mononuclear Cell Experimental Autoimmune Encephalomyelitis Cell Clone Myelin Basic Protein
Unable to display preview. Download preview PDF.
- Stinissen P, Medaer R, Raus J (1998a) Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis. Mult Scler 4: 203–211Google Scholar
- Stinissen P, Medaer R, Raus J (1998c) Preliminary data of an extended open label phase I study of T cell vaccination in multiple sclerosis. J Neuroimmunol 90: A564Google Scholar
- Waisman A, Ruiz PJ, Hirschberg DL, Gelman A, Oksenberg JR, Brocke S, Mor F, Cohen IR, Steinman L (1996) Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity. Nat Med 2: 899–905PubMedCrossRefGoogle Scholar
- Zhang JW, Markovic S, Lacet B, Raus J, Weiner HL, Hafler DA (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 179: 973–984.PubMedCrossRefGoogle Scholar