Functional maturation of proteolipid protein _139-151-specific Th1 cells in the central nervous system in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a widely adopted animal model system for studying human multiple sclerosis that affects the central nervous system (CNS). To understand the underlying pathogenic mechanisms of the autoimmune T cell response, localization, enumeration and characterization of autoreactive T cells are essential. We assessed encephalitogenic proteolipid protein epitope (PLP _139-151)-specific T cells in the periphery and CNS of SJL/J mice using MHC class II I-A ^s multimers during both pre-clinical and clinical phases of PLP-induced EAE in conjunction with T cell function. Our results strongly suggest that PLP _139-151-specific CD4 ⁺ T cells first expand primarily in the CNS-draining cervical lymph nodes and then migrate to the CNS. In the CNS, these PLP-specific CD4 ⁺ T cells accumulate, become activated and differentiate into effector cells that produce IFN-γ in response to the self-peptide.