Role of aging-associated Treg cell accumulation in experimental autoimmune encephalomyelitis (EAE) — a model of late-onset multiple sclerosis (MS)

Abstract

Abstract MS, a T cell-mediated autoimmune demyelinating disease of the central nervous system (CNS), has not been sufficiently studied in the elderly, despite instances of late-onset MS. Regulatory T (Treg) cells play an ameliorative role in MS disease onset and severity. Given that the aged immune system exhibits relatively enhanced thymic Treg cell generation and accumulated peripheral Treg cells, the role of Treg cell in aged MS patients remains to be elucidated. Using the mouse model EAE, we found that the aged mouse late-onset EAE occurs with two disease types. In Type I, EAE onset was delayed in the age mice, but the disease became more severe once onset. Alternatively, in Type II, some aged mice never developed severe symptoms than young mice until a second antigen challenge was given, which led to more a progressive disease course than their young counterparts. These features were potentially associated with a disparate distribution of Treg cells in the aged peripheral lymphoid tissues and CNS during the disease. The aged EAE mice had a higher proportion of polyclonal Treg cells in the peripheral lymphoid tissues, but a lower proportion of Treg cells specific for myelin oligodendrocyte glycoprotein (MOG) in the CNS, compared to young counterparts. Transient inhibition of accumulated polyclonal Treg cells in the periphery partially ameliorated disease severity in the aged mice, which was accompanied by increased MOG-specific Treg cells in the CNS. Therefore, we suggest that accumulated polyclonal Treg cells in the aged periphery are detrimental for CNS repair processes during neuronal inflammation in aged MS mice, potentially due to hampering trafficking of MOG-specific Treg cells into the CNS.