期刊
IMMUNOLOGY
卷 118, 期 3, 页码 384-391出版社
WILEY
DOI: 10.1111/j.1365-2567.2006.02385.x
关键词
EAE; T-bet; T-cells; IL-10; autoimmunity
类别
资金
- NINDS NIH HHS [NS-37766, NS-34741, NS-40144, NS-40810, NS-22576] Funding Source: Medline
Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin-specific CD4(+) T helper 1 (Th1) cells, while recovery from the disease is associated with the presence of Th2 cells. Here we used animals with targeted deletion of the T-bet gene to determine its role in the progression of EAE. T-bet regulates the production of interferon-gamma (IFN-gamma) in CD4(+) and natural killer cells, and CD4(+) T cells from T-bet-deficient mice were unable to differentiate into a Th1 phenotype. Moreover BALB/c mice deficient in T-bet were resistant to the induction of EAE disease, with minimal inflammatory infiltrates in the central nervous system. These mice were resistant to EAE induction even when PLP(180-199) peptide specific effector T cells from BALB/c wild type were transferred to BALB/c T-bet-deficient mice. This resistance to EAE is may be caused by the production of the anti-inflammatory cytokine interleukin-10 (IL-10) from the spleen cells upon ex vivo stimulation with PLP(180-199) peptide and in vivo presence in the central nervous system. There was no difference in the recall responses in spleen cells from T-bet-deficient and wild type mice; however, less secretion of IFN-gamma was observed from primed splenocytes. The expression of IFN-gamma was less in the central nervous system of T-bet-deficient mice whereas IL-10 was significantly higher in T-bet-deficient as compared to wild type mice. These data indicate that T-bet genes play a critical role in maintaining the encephalitogenic nature of CD4(+) T cells in autoimmune responses during EAE disease progression.
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