Chronological changes of CD4(+) and CD8(+) T cell subsets in the experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). The etiology of MS remains unclear, but T cells specific for myelin components, such as myelin oligodendrocyte glycoprotein (MOG), are thought to play a critical role in the onset of MS. Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of MS, and T helper type 1 (Th1) cells play an essential role for the pathogenesis of EAE through the production of Th1 cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). We examined CD4(+) and CD8(+) T cell responses in the spleen and CNS of EAE mice, generated by immunization with a peptide (35-55 amino acid residues) of MOG. The number of both CD4(+) and CD8(+) T cells and their MOG-reactivity in the CNS were associated with increasing disease severity but not those in the spleen, suggesting that the MOG-specific CD4(+) and CD8(+) T cells in the CNS are involved in the development of EAE. Polymerase chain reaction analysis suggested that both CD4(+) and CD8(+) T cells produced IFN-gamma and TNF-alpha, while CD4(+) T cells also produced interleukin-17 (IL-17), an important factor in the development of EAE. Thus, CD4(+) T cells may contribute to the induction of EAE by producing IL-17. Furthermore, CD8(+) T cells express higher levels of a suppressive cytokine, IL-10. Taking together, our data suggest that CD4(+) T cells are involved in the early phase of EAE, whereas CD8(+) T cells have a regulatory role in the later stage of EAE.
Sonobe
Yoshifumi
Y
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Jin
Shijie
S
Wang
Jinyan
J
Kawanokuchi
Jun
J
Takeuchi
Hideyuki
H
Mizuno
Tetsuya
T
Suzumura
Akio
A
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger