Zhang Xin, Xing Hanqian, Feng Xia, Zhang Haiping, Wang Yi, Yan Huiping
Virol J. 2013 Jul 12;10:232. doi: 10.1186/1743-422X-10-232.
Little is known about HBV-specific T-cell responses in chronic Hepatitis B patients (HBV) that are co-infected with Human immunodeficiency virus type 1 (HIV-1), especially those with normal alanine aminotransferase (ALT) levels.
Twenty-five patients with chronic HBV (11 hepatitis B e antigen [HBeAg]-positive, 14 HBeAg-negative) were enrolled in a cross-sectional study. A longitudinal study as also conducted in which follow-up was done at 3, 12, and 24 months, after acute HIV-1 infection, in 11 individuals who also had chronic HBV. Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein (S protein), core protein (C protein) or gag peptide. IFN-γ-secreting T cells were identified by ELISPOT assay.
In the cross-sectional study, co-infected chronic HBV patients had lower C protein-specific T-cell responses compared with mono-infected individuals, though the difference was not significant. In co-infected, chronic HBV patients, the magnitude of C protein-specific T-cell responses was significantly greater in HBeAg-positive subjects compared to HBeAg-negative subjects (p = 0.011). C protein-specific T-cell responses were positively correlated with HBV viral load (rs = 0.40, p = 0.046). However, gag-specific T-cell responses were negatively correlated with HIV viral load (rs = -0.44, p = 0.026) and positively correlated with CD4+ count (rs = 0.46, p = 0.021). The results were different in mono-infected individuals. PBMCs from co-infected HBeAg-positive patients secreted more specific-IFN-γ in cultured supernatants compared with PBMCs from co-infected HBeAg-negative patients (p = 0.019). In the longitudinal study, S protein- and C protein-specific T-cell responses were decreased as the length of follow-up increased (p = 0.034, for S protein; p = 0.105, for C protein). Additionally, the S protein- and C protein-specific T-cell responses were significantly higher in HBeAg-positive patients than in HBeAg-negative patients at 3 and 12 months after HIV-1 infection (all p < 0.05), but not at 24 months. A positive correlation (trend) was found between C protein-specific T-cell responses and HBV viral load at 3 and 12 months after HIV-1 infection.
HBV-specific T-cell responses to recombinant HBV core protein were reduced in chronic HBV patients co-infected with HIV-1. The reduced C protein-specific T cell responses were positively correlated with HBV viral load in co-infected, chronic HBV patients.
对于合并感染1型人类免疫缺陷病毒（HIV-1）的慢性乙型肝炎患者（HBV），尤其是丙氨酸氨基转移酶（ALT）水平正常的患者，其HBV特异性T细胞反应了解甚少。
25例慢性HBV患者（11例乙肝e抗原[HBeAg]阳性，14例HBeAg阴性）纳入一项横断面研究。还进行了一项纵向研究，对11例合并慢性HBV的个体在急性HIV-1感染后3、12和24个月进行随访。用重组HBV表面蛋白（S蛋白）、核心蛋白（C蛋白）或gag肽刺激外周血单个核细胞。通过酶联免疫斑点分析（ELISPOT）鉴定分泌干扰素-γ的T细胞。
在横断面研究中，与单一感染个体相比，合并感染的慢性HBV患者C蛋白特异性T细胞反应较低，尽管差异不显著。在合并感染的慢性HBV患者中，HBeAg阳性受试者的C蛋白特异性T细胞反应强度显著高于HBeAg阴性受试者（p = 0.011）。C蛋白特异性T细胞反应与HBV病毒载量呈正相关（rs = 0.40，p = 0.046）。然而，gag特异性T细胞反应与HIV病毒载量呈负相关（rs = -0.44，p = 0.026），与CD4 +细胞计数呈正相关（rs = 0.46，p = 0.021）。单一感染个体的结果不同。与合并感染的HBeAg阴性患者的外周血单个核细胞相比，合并感染的HBeAg阳性患者的外周血单个核细胞在培养上清液中分泌更多的特异性干扰素-γ（p = 0.019）。在纵向研究中，S蛋白和C蛋白特异性T细胞反应随着随访时间的延长而降低（S蛋白，p = 0.034；C蛋白，p = （此处原文有误，应为0.034）0.105）。此外，在HIV-1感染后3个月和12个月，HBeAg阳性患者的S蛋白和C蛋白特异性T细胞反应显著高于HBeAg阴性患者（所有p < 0.05），但在24个月时并非如此。在HIV-1感染后3个月和12个月，发现C蛋白特异性T细胞反应与HBV病毒载量之间存在正相关（趋势）。
合并感染HIV-1的慢性HBV患者对重组HBV核心蛋白的HBV特异性T细胞反应降低。在合并感染的慢性HBV患者中，降低的C蛋白特异性T细胞反应与HBV病毒载量呈正相关。
