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

Purpose: 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. Given that the aged immune system exhibits accumulated peripheral Treg (pTreg) cells, the role of Treg cell in aged MS patients remains to be elucidated. Methods: We immunized young and aged mice to induce EAE and investigated the disease courses and Treg cell associated mechanisms. Results: We found that the aged mice have two types of late-onset EAE. In Type I, EAE onset was delayed in the age mice, but the disease became more severe once after onset; Alternatively, in type II, some aged mice never developed into as severe symptoms as the young mice until a second antigen challenge was given, which led to more progressive disease courses than their young counterparts. This phenotype was potentially associated with a lower proportion of CNS-specific Treg cells in the aged CNS, even though the aged mice had a high proportion of polyclonal pTreg cells. Transient inhibition of polyclonal pTreg cells partially ameliorated the disease severity in the aged mice, accompanied with increased CNS-specific Treg cells in the CNS. Conclusions: Therefore, we suggest that accumulated polyclonal pTreg cells in the aged periphery are detrimental for CNS repair processes during neuronal inflammation in aged MS mice, potentially due to hampering trafficking of CNS-specific Treg cells into the CNS.