MHC class I and II expression and induction in oligodendrocytes varies with age

Oligodendroglia expressing major histocompatibility complex (MHC) molecules have become of central interest in multiple sclerosis (MS) research, but their role in aging is still being elucidated. Using MHC class I and II reporter mice, we compared oligodendroglial MHC expression in neonatal, young adult (8-16 weeks), and aging (52 weeks) mice at baseline and after stereotactic delivery of AAV-GFAP-IFNγ. We found that MHC class I-expressing oligodendroglia were present in both the naïve brain and spinal cord, while MHC class II-expressing oligodendroglia were seen only in the spinal cord of aging mice at baseline. After AAV injection, MHC expression in oligodendroglia increased, recapitulating pathology seen in MS mouse models and in MS post-mortem tissue. After IFNγ-AAV injection, the abundance of MHC class I-expressing oligodendroglia did not vary with age, whereas MHC class II-expressing oligodendroglia were more abundant in aging mice than neonatal and young adult mice. Our results suggest that MHC class II-expressing oligodendroglia are more prevalent with aging, which may contribute to the mechanisms underlying progressive MS and other age-related neurodegenerative diseases with central nervous system inflammation.