Altered T cell development in an animal model of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS), leading to demyelination and axonal degeneration. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that has significantly improved our understanding of MS. Studies have observed early thymic involution in MS patients, suggesting the potential involvement of the thymus in CNS autoimmunity. However, our knowledge of the thymus's role in autoimmune disorders affecting the CNS remains limited. In this study, we examined the effects of EAE induction on thymopoiesis and observed alterations in T cell development. These changes were characterized by increased apoptosis and decreased proliferation of thymocytes at the EAE peak stage. We also identified a blockade in the transition from CD4^-CD8^- double-negative thymocytes to CD4⁺CD8⁺ double-positive cells, as evidenced by the accumulation of double-negative stage 1 thymocytes at both the EAE onset and peak stages. Furthermore, positive selection was disrupted in the thymus of EAE mice at both stages, leading to an elevated proportion and number of CD4⁺CD8^- and CD4^-CD8⁺ single-positive cells. Meanwhile, we observed an augmented production of regulatory T cells in the thymus of EAE mice. Moreover, peripheral blood analysis of EAE mice at the onset stage showed expanded T cell subsets but not at the peak stage. We also observed altered expression patterns in thymus-derived CD4⁺CD8^- and CD4^-CD8⁺ single-positive cells between MS patients and healthy controls. Our findings demonstrate a modified T cell development in EAE/MS, providing valuable insights into the potential of modulating thymic function as a targeted therapeutic approach to MS/EAE.

Keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; T cell development; thymus.