Mutual activation of CD4+ T cells and monocytes mediated by NKG2D-MIC interaction requires IFN-gamma production in systemic lupus erythematosus.
Mutual activation of CD4+ T cells and monocytes mediated by NKG2D-MIC interaction requires IFN-gamma production in systemic lupus erythematosus.
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在系统性红斑狼疮中，NKG2D-MIC 相互作用介导的 CD4 T 细胞和单核细胞的相互激活需要产生 IFN-γ。
DOI：
10.1016/j.molimm.2008.12.010
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Wang H;Wang Q;Li J;Wu Y;Ni B;He Y;Xu G;Li K;Yang Z;Yang D;Fu X;Tang Y
活化受体NKG 2D主要由人CD 8 +T细胞和NK细胞表达，但通常在CD 4 +T细胞上不表达。然而，在一些自身免疫性疾病如类风湿性关节炎（RA）中，发现存在自身反应性NKG 2D + CD 4 +T细胞亚群，并参与免疫反应和炎症的失衡。到目前为止，这一观察结果已扩展到一些自身免疫性疾病，如RA和克罗恩病，这种类型的NKG 2D + CD 4 +T细胞存在的机制尚未阐明。在这项研究中，我们发现SLE患者PBMC中有相当比例的CD 4 +T细胞表达NKG 2D。我们还发现SLE患者的单核细胞在细胞表面异常表达NKG 2D配体的MHC I类链相关（MIC）分子和膜结合IL-15（mIL-15）。SLE患者血清可诱导健康人单核细胞表达MIC和mIL-15。然而，这种诱导的MIC和mIL-15的表达可被抗IFN-γ受体（抗IFN-γR）抗体阻断。我们进一步证明，与SLE患者的单核细胞或健康志愿者的单核细胞（但用IFN-γ预处理）共培养的正常CD 4 +T细胞均可诱导NKG 2D。此外，在共培养系统中，发现NKG 2D + CD 4 +T细胞产生Th 1细胞因子。通过transwell实验，我们发现NKG 2D的表达和Th 1细胞因子的产生都依赖于细胞间的接触。这些结果表明，血清IFN-γ升高可能是SLE中单核细胞MIC和mIL-15诱导的原因;单核细胞上的mIL-15有助于CD 4 +T细胞亚群上的NKG 2D受体诱导。此外，CD 14+单核细胞通过NKG 2D-MIC参与SLE发病机制促进NKG 2D + CD 4 +T细胞活化。
The activating receptor NKG2D is mainly expressed by human CD8+T cells and NK cells but normally absent on CD4+T cells. However, a subset of autoreactive NKG2D+CD4+T cells has been found to exist in some autoimmune disease such as rheumatoid arthritis (RA) and to participate in the imbalance of immune response and inflammation. Up to date this observation has been extended to some autoimmune diseases such as RA and Crohn's disease and the mechanism underlying the presence of this type of NKG2D+CD4+T cells has not been delineated yet. In this study, we found that a substantial proportion of CD4+T cells expressed NKG2D in the PBMC of SLE patients. We also found that monocytes in SLE aberrantly expressed the NKG2D ligand of MHC class I chain-related (MIC) molecules and membrane-bound IL-15 (mIL-15) at the cell surface. When cultured with the sera from SLE patients, the monocytes from healthy volunteers could be induced to express MIC and mIL-15. However, this induced expression of MIC and mIL-15 could be blocked with anti-IFN-γ receptor (anti-IFN-γR) antibody. We further demonstrated that NKG2D could be induced on normal CD4+T cells either cocultured with monocytes from patients with SLE, or monocytes from healthy volunteers but pretreated with IFN-γ. Moreover, Th1 cytokines were found to be produced by NKG2D+CD4+T cells in the coculture system. By transwell assay, we found that both NKG2D expression and Th1 cytokines production depended on the cell–cell contact. These results indicate that the elevated sera IFN-γ may be responsible for MIC and mIL-15 induction on monocytes in SLE; mIL-15 on monocytes contribute to NKG2D receptor induction on a subset of CD4+T cells. Moreover, CD14+monocytes promote NKG2D+CD4+T cells activation through the NKG2D–MIC engagement in the pathogenesis of SLE.
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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