Inoue M, Kakumu S, Yoshioka K, Tsutsumi Y, Wakita T, Arao M
Third Department of Medicine, Nagoya University School of Medicine, Japan.
J Immunol. 1989 Jun 1;142(11):4006-11.
To evaluate the specificity of cellular immune response to hepatitis B virus (HBV) Ag in patients with chronic HBV infection, we have measured IFN-gamma production and proliferation of PBMC of 16 patients with chronic active hepatitis (CAH), 17 asymptomatic carriers of HBV (ASC), 6 anti-hepatitis B surface (HBs)-positive subjects, and 6 control individuals with ELISA procedure and [3H]thymidine incorporation. There was no significant increase in the mean proliferative response to recombinant HB surface and core Ag (rHBsAg and rHBcAg), nor was IFN-gamma production elicited with rHBsAg in any group. In contrast, PBMC of HBeAg-positive and anti-HBe-positive CAH patients, and anti-hepatitis B "e" Ag (HBe)-positive ASC showed significantly enhanced IFN-gamma production in response to HBcAg, whereas those of HBeAg-positive ASC and anti-HBs-positive subjects did not respond to HBcAg. The maximal response was observed in a 5-day culture with 500 ng/ml of rHBcAg when assessed by stimulation index value. Monocytes did not demonstrate an increased suppressor or helper activity for IFN-gamma production in these patients. T cell subset fractionation revealed that CD4+ cells were main population of IFN-gamma production specific for HBcAg and CD8+ cells did not suppress IFN-gamma production of CD4+ cells. Furthermore, CD4+ cells of HBeAg-positive ASC generated lesser amounts of IFN-gamma than HBeAg-positive CAH patients did. These results show that the measurement of IFN-gamma production is useful to determine cellular immune response to HBV Ag and suggest that IFN-gamma production depends on the helper activity of CD4+ T cells sensitized to HBcAg.
为评估慢性乙肝病毒（HBV）感染者对乙肝病毒抗原的细胞免疫反应特异性，我们采用酶联免疫吸附测定法（ELISA）及[3H]胸腺嘧啶核苷掺入法，检测了16例慢性活动性肝炎（CAH）患者、17例无症状HBV携带者（ASC）、6例抗乙肝表面（HBs）阳性者及6例对照个体外周血单个核细胞（PBMC）的γ干扰素（IFN-γ）产生情况及增殖情况。对重组乙肝表面抗原和核心抗原（rHBsAg和rHBcAg）的平均增殖反应无显著增加，任何一组中rHBsAg均未诱导IFN-γ产生。相反，HBeAg阳性和抗-HBe阳性的CAH患者以及抗乙肝“e”抗原（HBe）阳性的ASC的PBMC对HBcAg刺激显示出显著增强的IFN-γ产生，而HBeAg阳性的ASC和抗-HBs阳性者的PBMC对HBcAg无反应。通过刺激指数值评估时，在含有500 ng/ml rHBcAg的5天培养中观察到最大反应。在这些患者中，单核细胞未显示出对IFN-γ产生的抑制或辅助活性增加。T细胞亚群分离显示，CD4+细胞是对HBcAg特异性产生IFN-γ的主要细胞群，CD8+细胞不抑制CD4+细胞的IFN-γ产生。此外，HBeAg阳性的ASC的CD4+细胞产生的IFN-γ量比HBeAg阳性的CAH患者少。这些结果表明，检测IFN-γ产生有助于确定对HBV抗原的细胞免疫反应，并提示IFN-γ产生取决于对HBcAg致敏的CD4+ T细胞的辅助活性。
