CD4 and CD8 T cells in susceptibility/protection to collagen-induced arthritis in HLA-DQ8-transgenic mice: Implications for rheumatoid arthritis
CD4 and CD8 T cells in susceptibility/protection to collagen-induced arthritis in HLA-DQ8-transgenic mice: Implications for rheumatoid arthritis
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DOI：
10.4049/jimmunol.168.11.5867
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
David, CS
中科院分区：
文献类型：
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作者：
Taneja, V;Taneja, N;David, CS
为了研究CD4和CD8T细胞在关节炎中的作用，我们培育了表达RA易感基因HLA-DQ8的CD4和CD8分子缺陷的转基因小鼠。DQ8、CD4(-/-)小鼠对胶原诱导性关节炎(CIA)具有抵抗力。然而，与DQ8(-/-)小鼠相比，DQ8(-/-)小鼠发生CIA的发生率和严重程度都有所增加。DQ8、CD8(-/-)和DQ8小鼠均产生类风湿因子。此外，DQ8.CD8(-/-)小鼠产生抗核抗体。所有品系的B细胞亚群和DQ8的表达均正常，但在CD4(-/-)小鼠中表达DQ8的细胞频率较低。DQ8(-/-)组CD3(+)双阴性(DN)T细胞比例高于DQ8(-/-)组和DQ8(-/-)组。这些CD3(+)dN T细胞在CD8缺陷小鼠体内产生高水平的IL-10。使用细胞周期跟踪染料对细胞分裂的分析表明，DQ8(-/-)小鼠的CD3(+)和CD3(+)dN T细胞的分裂率高于DQ8(-/-)和DQ8小鼠。在CIA敏感的DQ8和CD8缺陷小鼠中，细胞凋亡减少，这表明激活诱导的细胞死亡存在缺陷。这些观察结果表明，在DQ8小鼠中，CD4细胞是启动CIA所必需的。我们推测CD8(+)T细胞不能在DQ8转基因小鼠中启动CIA，但可能具有调节/保护作用。
To investigate the role of CD4 and CD8 T cells in arthritis, we generated transgenic mice deficient in CD4 and CD8 molecules expressing RA-susceptible gene HLA-DQ8. DQ8.CD4(-/-) mice were resistant to developing collagen-induced arthritis (CIA). However, DQ8.CD8(-/-) mice developed CIA with increased incidence and more severity than DQ8 mice. Both DQ8.CD8(-/-) and DQ8 mice produced rheumatoid factor. In addition, DQ8.CD8(-/-) mice produced antinuclear Abs. The B cell compartment and expression of DQ8 were normal in all the strains, although frequency of cells expressing DQ8 was less in CD4(-/-) mice. An increased frequency of CD3(+) double-negative (DN) T cells was found in DQ8.CD8(-/-) compared with DQ8.CD4(-/-) and DQ8 mice. These CD3(+) DN T cells produced high amounts of IL-10 in CD8-deficient mice. Analysis of cell division using a cell cycle tracking dye showed a higher rate of division of CD3(+) and CD3(+) DN T cells in DQ8.CD8(-/-) mice compared with DQ8.CD4(-/-) and DQ8 mice. Decreased apoptosis was seen in CIA-susceptible DQ8 and CD8-deficient mice, indicating a defect in activation-induced cell death. These observations suggest that CD4 cells are necessary for initiation of CIA in DQ8 mice. We hypothesize that CD8(+) T cells are not capable of initiating CIA in DQ8-transgenic mice but may have a regulatory/protective effect.