Sanna A, Huang Y M, Arru G, Fois M L, Link H, Rosati G, Sotgiu S
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy.
Mult Scler. 2008 Nov;14(9):1199-207. doi: 10.1177/1352458508094401. Epub 2008 Jul 24.
We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses.
We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN-gamma), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-alpha and beta, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1).
The subset of lineage negative (lin(-)), BDCA-2(+) cells was lower in patients with MS compared with HC (0.08 + or - 0.02% vs 0.24 + or - 0.02%; P < 0.001). A similar pattern was observed for lin(-)BDCA-4(+) cells (0.08 + or - 0.02% vs 0.17% + or - 0.03; P < 0.01). Spontaneous productions of IL-6 (45 + or - 10 pg/mL vs 140 + or - 26 pg/mL; P < 0.01) and IL-10 (17 + or - 0.4 pg/mL vs 21 + or - 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 + or - 0.15 pg/mL vs 21 + or - 5 pg/mL; P < 0.01 and IL-10 (11 + or - 1 pg/mL vs 14 + or - 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN-alpha, IL-6, and IL-10 but decreased production of IL-4. In response to HSV-1 exposure, productions of IL-6 (165 +or - 28 pg/mL vs 325 + or - 35 pg/mL; P < 0.01) and IL-10 (27 +or - 3 vs 33 + or - 3 P < 0.05) by MNC as well as by pDC (IL-6: 28 + or - 7 vs 39 + or - 12 P < 0.05; IL-10: 14 + or - 1 vs 16 + or - 3 P < 0.05) were lower in patients with MS compared with HC.
The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.
我们推测在多发性硬化症（MS）中观察到的自身攻击性免疫反应可能与免疫细胞亚群比例失衡以及对包括病毒在内的感染产生的细胞因子失衡有关。
我们从意大利撒丁岛收集了23例MS患者和23例年龄及性别匹配的健康对照（HC）的血液单核细胞（MNC），该岛MS患病率极高。使用流式细胞术，我们研究了MNC中血液树突状细胞抗原（BDCA）-2和BDCA-4表面标志物的表达，这些标志物反映了浆细胞样树突状细胞（pDC）的比例，pDC在病毒攻击后产生I型干扰素（IFN）并促进Th2/抗炎细胞因子的产生。同时，在体外暴露于1型单纯疱疹病毒（HSV-1）之前和之后，测量促炎（白细胞介素[IL]-2、IL-12、IFN-γ）、抗炎（IL-4、IL-10）和免疫调节/多效性细胞因子（包括IFN-α和β的I型IFN、IL-6）。
与HC相比，MS患者中谱系阴性（lin(-)）、BDCA-2(+)细胞亚群更低（0.08±0.02%对0.24±0.02%；P<0.001）。lin(-)BDCA-4(+)细胞也观察到类似模式（0.08±0.02%对0.17%±0.03；P<0.01）。与HC相比，MS患者MNC自发产生的IL-6（45±10 pg/mL对140±26 pg/mL；P<0.01）和IL-10（17±0.4 pg/mL对21±1 pg/mL；P<0.05）更低。与HC相比，MS患者pDC自发产生的IL-6（6.5±0.15 pg/mL对21±5 pg/mL；P<0.01）和IL-10（11±1 pg/mL对14±3 pg/mL；P<0.05）也更低。MNC暴露于HSV-1后，在MS患者和HC中均显示IFN-α、IL-6和IL-10产生增加，但IL-4产生减少。与HC相比，MS患者MNC以及pDC对HSV-1暴露的反应中IL-6（165±28 pg/mL对325±35 pg/mL；P<0.01）和IL-10（27±3对33±3 P<0.05）的产生更低（IL-6：28±7对39±12 P<0.05；IL-10：14±1对16±3 P<0.05）。
结果表明MS中免疫细胞改变及对病毒攻击的免疫反应降低有了新证据。
