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在健康对照者和接受抗逆转录病毒治疗且无病毒血症的HIV感染者中,季节性流感疫苗接种后B细胞上CD80和凋亡的诱导以及CD4+T细胞中CD40L的表达,可区分应答者和无应答者。

The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals.

作者信息

Powell Anna M, Luo Zhenwu, Martin Lisa, Wan Zhuang, Ma Lei, Liao Guoyang, Song Yuxia, Li Xiaochun, Michael Kilby J, Huang Lei, Jiang Wei

机构信息

Department of Obstetrics and Gynecology, Medical University of South Carolina, 29425, USA.

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425, USA.

出版信息

Vaccine. 2017 Feb 1;35(5):831-841. doi: 10.1016/j.vaccine.2016.12.026. Epub 2016 Dec 22.

Abstract

BACKGROUND

Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART).

METHODS

16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7-10 (D7) and 14-21 (D14) following the 2013-2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ⩾4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry.

RESULTS

9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status.

CONCLUSION

The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness.

摘要

背景

研究表明,HIV感染与流感疫苗反应受损有关。我们研究了细胞表型和功能在接受抗逆转录病毒治疗(ART)的健康对照者和无病毒血症的HIV感染者对流感疫苗反应中的作用。

方法

16名健康对照者和26名接受ART治疗且无病毒血症的HIV感染者参与了本研究。在接种2013 - 2014年季节性流感疫苗前(D0)、接种后第7 - 10天(D7)和第14 - 21天(D14)采集血液。如果在D14时针对H1N1病毒的中和滴度相较于D0增加≥4倍,则将受试者分类为反应者。在D0和D7通过流式细胞术对B细胞和CD4 + T细胞频率及活化进行系列分析。

结果

26名HIV感染者中有9名(34.6%)、16名健康对照者中有7名(43.8%)被分类为流感疫苗反应者。在接种疫苗后的D7,无论是对照组还是HIV +受试者,无反应者的总B细胞凋亡(膜联蛋白V)增加,而反应者未增加。在对照组反应者的D7,记忆B细胞表面CD80表达和记忆CD4 + T细胞内CD40L表达被诱导,而无反应者未出现。无论反应者和无反应者,HIV感染者均未出现CD80和CD40L诱导。四个研究组中记忆CD4 + T细胞周期在D7均有增加趋势,但未达到显著水平。无论HIV感染状态如何,反应者和无反应者之间的所有其他参数均无差异。

结论

无反应者和HIV感染者在季节性流感疫苗接种后B细胞或CD4 + T细胞活化和凋亡诱导的扰动可能有助于理解疫苗反应受损的机制。

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