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学龄前儿童中百日咳特异性效应记忆T细胞的鉴定

Identification of pertussis-specific effector memory T cells in preschool children.

作者信息

de Rond Lia, Schure Rose-Minke, Öztürk Kemal, Berbers Guy, Sanders Elisabeth, van Twillert Inonge, Carollo Maria, Mascart Françoise, Ausiello Clara M, van Els Cecile A C M, Smits Kaat, Buisman Anne-Marie

机构信息

Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

出版信息

Clin Vaccine Immunol. 2015 May;22(5):561-9. doi: 10.1128/CVI.00695-14. Epub 2015 Mar 18.

Abstract

Whooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4(+) and CD8(+) T-cell fractions (CFSE(dim)) were higher in aP- than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4(+) effector memory cells (CD45RA(-) CCR7(-)) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP- and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4(+) and CD8(+) effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

摘要

尽管有疫苗接种,百日咳仍是一个问题,并且百日咳在全球范围内明显出现了复发。由于细胞免疫在长期预防百日咳中发挥作用,我们研究了百日咳特异性T细胞反应。在4岁进行学龄前无细胞百日咳(aP)加强免疫时,比较了婴儿期接种全细胞百日咳(wP)疫苗或aP疫苗的儿童的T细胞记忆反应。分离外周血单核细胞(PBMC),并用百日咳疫苗抗原刺激5天。通过基于流式细胞术分析羧基荧光素琥珀酰亚胺酯(CFSE)稀释度以及CD4、CD3、CD45RA、CCR7、γ干扰素(IFN-γ)和肿瘤坏死因子α(TNF-α)表达来鉴定T细胞。在aP学龄前加强免疫之前,aP初免儿童中增殖的百日咳毒素(PT)特异性CD4(+)和CD8(+) T细胞亚群(CFSE(dim))比例高于wP初免儿童。加强免疫后,aP初免儿童比wP初免儿童诱导产生更多的百日咳特异性CD4(+)效应记忆细胞(CD45RA(-) CCR7(-))。加强免疫似乎对aP初免或wP初免儿童的T细胞记忆亚群和功能没有显著影响。尽管在加强免疫前aP初免和wP初免儿童中产生Th1细胞因子的细胞百分比相似,但由于增殖的百日咳特异性效应记忆细胞数量更多,aP初免儿童产生更多的Th1细胞因子。目前,在生命的第一年接种四剂aP疫苗可使儿童产生百日咳特异性CD4(+)和CD8(+)效应记忆T细胞反应,这些反应可持续到4岁,并且高于wP初免儿童。因此,4岁时的加强免疫值得怀疑;这可能推迟到6岁。

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