Zhou Yali, Zhang Hong, Li Yumin
Central Laboratory, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, PR China; Gansu Provincial Key Laboratory of Digestive System Tumors, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, PR China.
Clinical Laboratory, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, PR China.
Cytokine. 2015 May;73(1):169-75. doi: 10.1016/j.cyto.2015.02.003. Epub 2015 Mar 6.
Interleukin 35 (IL-35) functions in an anti-inflammatory fashion by inhibiting T-cell proliferation, whereas CD4(+) T cells play an important role in cellular immunity. In a hepatitis B virus (HBV) infection, the viral proteins stimulate the immune system to generate antiviral molecules, which correlate to HBV DNA load. We investigated the impact of HBV DNA load on the expression of IL-35 mRNA in CD4(+) T cells, and the expression of IL-35 cytokine in serum of the patients with chronic HBV infection. Here we report that the frequency of circulating CD4(+) T cells correlates with the HBV DNA load in the serum of chronic hepatitis B (CHB) patients. An increased number of CD4(+) T cells were found in those patients with higher levels of HBV DNA. Regulatory T cells (T regs) also showed this trend, but circulating cytotoxic lymphocytes (CTLs) showed a negative correlation with serum HBV DNA load. In addition, significantly more IL-35 mRNA was found in the CD4(+) T cells of CHB patients, compared to healthy controls. Patients in the high viral load group showed increased levels of IL-35 mRNA, compared with those in the low viral load group. The level of IL-35 cytokine in the serum of CHB patients was significantly higher than in the healthy controls and in those infected with HBV, the patients with a higher viral load had more serum IL-35 cytokines, compared to those with a lower viral load. Our study suggests that increased serum IL-35 could be directly related to increased levels of IL-35 mRNA in CD4(+) T cells and HBV DNA load in CHB patients. The possible role of IL-35 as an immune regulator in chronic HBV infection should be investigated further.
白细胞介素35（IL-35）通过抑制T细胞增殖发挥抗炎作用，而CD4(+) T细胞在细胞免疫中起重要作用。在乙型肝炎病毒（HBV）感染中，病毒蛋白刺激免疫系统产生抗病毒分子，这些分子与HBV DNA载量相关。我们研究了HBV DNA载量对慢性HBV感染患者CD4(+) T细胞中IL-35 mRNA表达以及血清中IL-35细胞因子表达的影响。在此我们报告，慢性乙型肝炎（CHB）患者血清中循环CD4(+) T细胞的频率与HBV DNA载量相关。在HBV DNA水平较高的患者中发现CD4(+) T细胞数量增加。调节性T细胞（Tregs）也呈现这种趋势，但循环细胞毒性淋巴细胞（CTLs）与血清HBV DNA载量呈负相关。此外，与健康对照相比，CHB患者的CD4(+) T细胞中发现的IL-35 mRNA明显更多。高病毒载量组患者的IL-35 mRNA水平高于低病毒载量组患者。CHB患者血清中IL-35细胞因子水平明显高于健康对照，并且在感染HBV的患者中，病毒载量较高的患者血清IL-35细胞因子比病毒载量较低的患者更多。我们的研究表明，血清IL-35升高可能与CHB患者CD4(+) T细胞中IL-35 mRNA水平升高和HBV DNA载量增加直接相关。IL-35作为慢性HBV感染中免疫调节因子的可能作用应进一步研究。
