期刊
JOURNAL OF CLINICAL IMMUNOLOGY
卷 29, 期 4, 页码 426-433出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-009-9287-7
关键词
EAE; ICOS; MOG; IL-17; Th17
类别
Inducible costimulatory molecule (ICOS) is important for the effector function of T cells, especially for Th2 and T cell dependent B cell responses. However, it has been shown that ICOS is required for the differentiation of Th17 cells. Since IL-17 has been identified as a major cytokine involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the enhanced severity of EAE in ICOS-deficient mice (ICOS-/-) mice is unexpected. To better understand the role of ICOS and of IL-17 in EAE, we induced EAE in ICOS-/- by immunization with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)) in complete Freund's adjuvant. As previously reported, we found that ICOS-/- mice developed more severe EAE. Upon restimulation with MOG(35-55,) splenocytes from ICOS-/- mice with EAE produced higher amounts of IL-17 and ICOS-/- mice had a higher expression of IL-17, IL-6, and TGF-beta mRNA in the spinal cords at the onset of the disease. Finally, the blockade of IL-17 strongly inhibited disease even in ICOS-/- mice, showing that IL-17 is playing a major role in the pathogenesis of EAE both in WT and ICOS-/- mice. In conclusion, MOG immunization induces MOG-specific Th17 cells also in ICOS-/- mice, and a higher expression of IL-17 and of Th17-driving cytokines IL-6 and TGF-beta in the central nervous system at the onset of EAE that correlates with their more severe disease.
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