AI Article Synopsis
- Experimental autoimmune encephalomyelitis (EAE) is a model for studying multiple sclerosis, mainly using Lewis rats and various murine models, but this study introduces a new model using Wistar rats and guinea pig spinal cord antigens.
- The study found that autoreactive T cells could be completely inhibited in vitro using CTLA4Ig, which blocks T cell costimulation, but this inhibition could be reversed with the addition of IL-2.
- Additionally, CTLA4Ig treatment reduced the expression of IL-2 receptors and T cell activity while not affecting IL-10 synthesis, supporting the idea that B7-blocking therapies could be a potential treatment for multiple sclerosis.
Article Abstract
Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis that requires the activation of autoreactive T cells for the expression of pathology. EAE has been most frequently studied in the Lewis rat model as well as in several murine models of EAE including the PLJ and B10PL strains. In the present study we describe a novel model of EAE induced in the Wistar rat strain by immunization with guinea pig spinal cord antigens and pertussis toxin (PT). T cell responses were induced to myelin basic protein. Autoreactive T cells could be totally blocked by the in vitro treatment with CTLA4Ig, a protein that blocks the costimulation of autoreactive T cells. The addition of IL-2 could reverse the inhibition seen in vitro with CTLA4Ig. The effects of inhibition of B7 costimulation were also examined by an analysis of cytokine responses and IL-2 receptor on T cells. CTLA4Ig treatment in vitro reduced the expression of IL-2 receptor on T cells, enhanced T cell apoptosis and decreased the synthesis of IL-2, IFN-gamma and TNF-alpha. CTLA4Ig treatment had no effect on IL-10 synthesis by T cells, a cytokine implicated in the functions of regulatory T cell subsets. Overall, our studies support the rationale of B7 blocking therapies as a potential treatment for models of multiple sclerosis. The induction of EAE in the Wistar rat provides yet another novel model in which to examine the regulation of T cell autoimmunity.
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| http://dx.doi.org/10.1080/08916930290024160 | DOI Listing |
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