Aged T cells shape neuronal autoimmune disease in a model of late-onset multiple sclerosis (Supported by NIH/NIAID R01AI121147)

Abstract

Abstract Although multiple sclerosis (MS), a T cell-mediated autoimmune demyelinating disease, mainly develops in young people, late-onset has also been observed in aged people. The aged T cell immune system is different from the young. One of characteristics is disrupted thymocyte negative selection, and relatively enhanced thymic regulatory T (tTreg) cell generation and accumulated peripheral Treg (pTreg) cells. The relatively increased polyclonal Treg cells potentially shape the MS disease courses, and may even prevent remission stages of this disease. Using the mouse model experimental autoimmune encephalomyelitis (EAE) of human MS, we determined that a late-onset EAE has two types of disease courses. I: Onset of EAE in the aged group was later than the young group, but after onset, the disease became more severe than in their young counterparts; II: Alternatively, onset of EAE in the aged group never became severe until after a second antigen challenge was given, causing the symptoms to appear and progress to severe disease much faster than in their young counterparts. We also found that this late-onset of EAE was associated with a disparate distribution of Treg cells in lymph nodes versus in the central nervous system (CNS) during the disease. The aged mice had a high proportion of pTreg cells in the lymph nodes, but a low proportion in the CNS, compared to their young counterparts. We believe that accumulated pTreg cells in the elderly, which is one of hallmarks of aged T cell immune system, potentially results in their residing in the blood-brain barrier and/or choroid plexus, which hampers trafficking of monocytes and/or antigen-specific Treg cells into the CNS. Thus, it is detrimental for a CNS repairing processes in neuronal inflammation.