Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy
Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy
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DOI：
10.1172/jci119455
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发表时间：
1997-06-01
影响因子：
15.9
通讯作者：
Reder, AT
中科院分区：
文献类型：
--
作者：
Genc, K;Dona, DL;Reder, AT
共刺激分子有助于确定T细胞应答，CD 80（B7-1）和CD 86（B7-2），抗原呈递细胞上的共刺激蛋白，与T细胞上的CD 28结合。当共刺激与通过T细胞受体（TCR）的信号偶联时，诱导T细胞增殖和细胞因子分泌。在多发性硬化症（MS）恶化期间，循环免疫细胞被激活，血液中Th 1细胞因子水平升高，血液来源的免疫细胞破坏脑少突胶质细胞。在MS的实验性自身免疫性脑脊髓炎模型中，抗原呈递细胞上的CD 80诱导Th 1细胞应答; CD 86增强Th 2细胞的产生。CD 80和CD 86表达的变化可能会影响MS的免疫调节。我们证明，循环中的CD 80（+）淋巴细胞的数量在MS急性加重期间显著增加，但在稳定的MS中是正常的。这些CD 80（+）淋巴细胞主要是B细胞，基于双色流式细胞术。在活动性MS中，CD 71（+）和HLA-DR+淋巴细胞和单核细胞的数量也增加。用IFN β-Ib治疗显著降低循环中CD 80（+）B细胞的数量，并增加CD 86（+）单核细胞的数量。HLA-DR+、CD 71（+）和CD 25（+）单核细胞数量也通过治疗减少。CD 80（+）细胞的数量可能是IFN-β治疗期间有用的替代标志物，并且CD 80介导的共刺激减少可能是IFN-β在MS中起作用的一种治疗机制。
Costimulatory molecules help determine T cell responses, CD80 (B7-1) and CD86 (B7-2), costimulatory proteins on antigen-presenting cells, bind to CD28 on T cells. When costimulation is coupled with a signal through the T cell receptor (TCR), T cell proliferation and cytokine secretion are induced. However, TCR signaling without CD80/CD86-CD28 costimulation causes anergy.During multiple sclerosis (MS) exacerbations, circulating immune cells are activated, Th1 cytokine levels in the blood are elevated, and blood-derived immune cells destroy brain oligodendroglia. In the experimental autoimmune encephalomyelitis model of MS, CD80 on antigen-presenting cells induces Th1 cell responses; CD86 enhances generation of Th2 cells. Variation in CD80 and CD86 expression is likely to influence immune regulation in MS.We demonstrate that the number of circulating CD80(+) lymphocytes is increased significantly during MS exacerbations, but is normal in stable MS. These CD80(+) lymphocytes are predominantly B cells, based on two-color flow cytometry. The number of CD71(+) and HLA-DR+ lymphocytes and monocytes is also increased in active MS,Therapy with IFN beta-lb markedly reduces the number of circulating CD80(+) B cells and increases CD86(+) monocyte number. HLA-DR+, CD71(+), and CD25(+) mononuclear cell numbers are also reduced by therapy, The number of CD80(+) cells may be a useful surrogate marker during IFN-beta therapy, and reduction of CD80-mediated costimulation may be one therapeutic mechanism by which IFN-beta acts in MS.