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.