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两剂候选减毒活登革病毒疫苗接种者的血清型特异性T(H)1反应

Serotype-specific T(H)1 responses in recipients of two doses of candidate live-attenuated dengue virus vaccines.

作者信息

Gwinn William, Sun Wellington, Innis Bruce L, Caudill Jeffrey, King Alan D

机构信息

Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.

出版信息

Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):39-47. doi: 10.4269/ajtmh.2003.69.39.

DOI:10.4269/ajtmh.2003.69.39
PMID:14740954
Abstract

As part of a larger vaccine study, peripheral blood mononuclear cells (PBMC) were collected from volunteers for analysis of vaccine-induced T cell responses. The PBMC were re-stimulated in vitro with live dengue virus and assayed for T(H)1 or T(H)2 memory cell responses. Re-stimulated PBMC from the volunteers predominantly secreted interferon-gamma. Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a T(H)1 type of T cell response. The interferon-gamma response was primarily serotype-specific with some serotype cross-reactivity. T cell depletion studies showed that the interferon-gamma was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes. CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes. However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes. In summary, an antigen-specific T(H)1 type T cell response was seen as a response to vaccination using live attenuated dengue virus.

摘要

作为一项规模更大的疫苗研究的一部分,从志愿者身上采集外周血单核细胞(PBMC),用于分析疫苗诱导的T细胞反应。PBMC在体外经活登革病毒再次刺激,并检测其Th1或Th2记忆细胞反应。志愿者再次刺激后的PBMC主要分泌干扰素-γ。几乎未检测到白细胞介素-4(IL-4)或IL-10的分泌,表明是Th1型T细胞反应。干扰素-γ反应主要具有血清型特异性,存在一些血清型交叉反应性。T细胞耗竭研究表明,干扰素-γ由CD4 + T淋巴细胞和/或受CD4 + T淋巴细胞刺激的CD8 + T淋巴细胞以外的细胞分泌。CD3 +或CD8 + T细胞耗竭表明,颗粒酶B mRNA表达与CD4 + T淋巴细胞的存在相关。然而,刺激四天后CD4 + T细胞的耗竭表明,颗粒酶B mRNA是由培养物中淋巴细胞以外的细胞产生的。总之,使用减毒活登革病毒进行疫苗接种后,可观察到抗原特异性Th1型T细胞反应。

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