Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen
Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen
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DOI：
10.1016/s0264-410x(00)00084-0
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发表时间：
2000-07-01
期刊：
影响因子：
5.5
通讯作者：
Alper, CA
中科院分区：
文献类型：
--
作者：
Larsen, CE;Xu, JH;Alper, CA
一些接种了B型肝炎表面抗原（HBsAg）的人类受试者不产生疫苗抗体（无应答者）。无应答的机制尚不清楚。为了更好地理解对标称抗原的应答和无应答，我们测定了来自HBsAg疫苗应答者和无应答者以及来自HBsAg初治个体的外周血金色单核细胞（PBMC）对HBsAg和破伤风环状体（TT）应答的细胞因子分泌水平和动力学，体外培养PBMC在第2天分泌最高水平的白细胞介素-2（IL-2）和最高水平的肿瘤坏死因子-β在刺激后3-6天，检测细胞因子（TNF-β）、干扰素-γ（IFN-γ）、IL-4和IL-10。相比之下，非增殖PBMC（无论来自无应答者、幼稚受试者还是弱应答者）不产生可检测水平的TNF-β或IFN-γ，也不显著产生IL-4或IL-10，并且所产生的具有与增殖PBMC不同的动力学特征。来自强应答者的PBMC产生的HBeAg特异性细胞因子广泛地抑制了其对TT的细胞因子应答。通过逆转录-聚合酶链反应测定的细胞细胞因子mRNA水平证实了分泌的细胞因子结果。抗-HBsAg-和抗-TT-特异性T细胞细胞因子应答是混合的Th-1/2样和供体特异性。在无应答者中完全缺失了HBeAg特异性细胞因子应答，而不是TT特异性细胞因子应答。这些数据表明，HBsAg无应答的T细胞缺陷不是由于细胞因子谱的偏斜。(C)2000爱思唯尔科技有限公司版权所有。
Some human subjects vaccinated with hepatitis B surface antigen (HBsAg) do not produce antibodies to the vaccine (nonresponders). The mechanism for nonresponse is unknown. To understand the response and nonresponse to nominal antigens better, we determined the level and kinetics of cytokine secretion in response to HBsAg and tetanus toroid (TT) by peripheral blond mononuclear cells (PBMC) in vitro from HBsAg vaccine responders and nonresponders and from individuals naive to HBsAg, Proliferating PBMC secreted peak levels of interleukin-2 (IL-2) at 2 days and peak levels of tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), IL-4 and IL-10 at 3-6 days post-stimulation. In contrast, nonproliferating PBMC (whether from nonresponders, naive subjects or weak responders) did not produce detectable levels of TNF-beta or IFN-gamma, nor was IL-4 or IL-10 produced significantly, and that produced had a different kinetic profile from that of proliferating PBMC. HBsAg-specific cytokine production by PBMC from strong responders broadly paralleled their cytokine responses to TT. Cellular cytokine mRNA levels measured by reverse transcriptase-polymerase chain reaction corroborated the secreted cytokine results. The anti-HBsAg- and anti-TT-specific T cell cytokine responses were mixed Th-1/2-like and donor-specific. An HBsAg-specific cytokine response, but not a TT-specific cytokine response, was completely missing in nonresponders. These data suggest that the T cell defect of HBsAg nonresponse is not due to a skewed cytokine profile. (C) 2000 Elsevier Science Ltd. All rights reserved.