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 T(H)1 cells in particular the T(H)17 subset is believed to be highly pathogenic. Spreading of the T(H)1 and T(H)17 response to newly emerging determinants has been used to explain clinical disease relapse, but if the magnitude of the T(H)1/T(H)17 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 T(H)1/T(H)17 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.
Department of Anatomy I, University Hospitals of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
Helena
H
Batoulis
Martin
M
Uhl
Klaus
K
Addicks
Paul V
PV
Lehmann
Stefanie
S
Kuerten
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D051379:Mice; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology*
D018984:Epitopes, T-Lymphocyte