The magnitude of the antigen-specific T cell response is separated from the severity of spinal cord histopathology in remitting-relapsing experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. The remitting-relapsing experimental autoimmune encephalomyelitis (EAE) in the SJL mouse strain is a common animal model for MS and similar to the human disease it is considered to be T helper cell mediated. Besides interferon-γ secreting TH1 cells in particular the TH17 subset is believed to be highly pathogenic. Spreading of the TH1 and TH17 response to newly emerging determinants has been used to explain clinical disease relapse, but if the magnitude of the TH1/TH17 response is linked to clinical relapse severity has remained unresolved. Here, we assessed clinical EAE severity, the extent of spinal cord histopathology and the magnitude of the antigen-specific T helper cell and autoantibody response in proteolipid protein peptide 139–151 (PLP:139–151)-immunized SJL mice in clinical remission and relapse. We demonstrate that spinal cord histopathology comprised inflammation, demyelination as well as axonal loss and correlated well with clinical disease severity. Although the degree of spinal cord histopathology and clinical severity was separated from the PLP:139–151-specific TH1/TH17 cell and antibody response, it was linked to the number of infiltrating macrophages and activated microglia. In particular, there was a correlation between their secretion product interleukin-1β and the degree of axonal loss. Although CD4+ T cells seem to be mainly involved in disease initiation, we suggest that it is the downstream activation of the innate immune response that defines the magnitude of the disease outcome. © 2012 Wiley Periodicals, Inc.