Aged T cell immune system aggravates late-onset experimental autoimmune encephalomyelitis

Purpose: human multiple sclerosis (MS) mirrored by a mouse model experimental autoimmune encephalomyelitis (EAE) is autoreactive conventional T (Tcon) cell-mediated neuroinflammatory diseases, while regulatory T (Treg) cells can slow the disease. Although MS mostly attacks young adults, its onset is also observed in aged people, termed late-onset MS, which presents a severer progression and more neurological damages, under the aged aberrant T cell immune milieus. However, it is unknown how aged T cells contribute to late-onset MS and what are the underlying mechanism(s). Methods: We use mouse EAE model by immunizing young and aged mice to induce EAE and investigated the disease course and the profiles of Tcon versus Treg cells inside and outside of the central nervous system (CNS). Results: We determined that aged mice had two types of EAE courses, different from the young mice. Type-I: EAE onset in aged group is later than, but rapidly becomes more severe than the young group; Type-II: in some aged mice the severity of EAE symptoms was never stronger than in young mice. However, once the secondary challenge is applied, their symptoms develop faster and are more severe than their young counterparts. Treg cells are accumulated in the peripheral lymphoid organs in aged EAE mice, but not efficiently infiltrating or expanding inside the CNS to restore neuroinflammation. Conclusions: Even though Treg cells are accumulated in the aged periphery, the CNS infiltrated Treg cells are decreased, which are insufficient to protect neurological damages in late-onset EAE.