Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans
Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans
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DOI：
10.1002/eji.201746974
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发表时间：
2017-06-01
影响因子：
5.4
通讯作者：
Goodier, Martin R.
中科院分区：
文献类型：
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作者：
Darboe, Alansana;Danso, Ebrima;Goodier, Martin R.
人巨细胞病毒 (HCMV) 感染会驱动 NK 细胞的表型和功能分化，从而影响这些细胞在接种疫苗后的反应。 NK 细胞功能分化在普遍接触 HCMV 的非洲人群中尤其先进。为了研究晚期分化对疫苗诱导反应的影响，我们研究了普遍终身接触 HCMV 的非洲人接种三价流感疫苗 (TIV) 或白喉、破伤风、百日咳、灭活脊髓灰质炎病毒疫苗 (DTPiP) 前后的 NK 细胞功能。与HCMV感染率较低的人群相比，与接种前的基线细胞相比，用TIV或DTPiP抗原体外再刺激接种后的NK细胞后，NK细胞反应（IFN-γ、CD107a、CD25）没有显着增强。然而，两种疫苗均导致 NK 细胞响应外源性 IL-12 和 IL-18 产生 IFN-γ 的频率更高，这种情况可持续长达 6 个月。细胞因子反应性增强仅限于分化程度较低的 NK 细胞，在 CD56(bright)CD57(-)、CD56(dim)CD57(-)NKG2(-) 和 CD56(dim)CD57(-)NKG2C(+) NK 细胞亚群中观察到 IFN-gamma(+) 细胞频率增加。这些数据表明了一种共同的机制，不同的疫苗可以增强 HCMV 感染供体中的 NK 细胞 IFN-γ 功能，并提高了进一步利用 NK“细胞预激活”来提高疫苗有效性的潜力。
Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-gamma, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-gamma in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-gamma(+) cells observed within CD56(bright)CD57(-), CD56(dim)CD57(-)NKG2(-) and CD56(dim)CD57(-)NKG2C(+) NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-gamma function in HCMV infected donors and raise the potential for further exploitation of NK "cellpre-activation" to improve vaccine effectiveness.