Frequencies of Circulating MAIT Cells Are Diminished in Chronic HCV, HIV and HCV/HIV Co-Infection and Do Not Recover during Therapy.
Frequencies of Circulating MAIT Cells Are Diminished in Chronic HCV, HIV and HCV/HIV Co-Infection and Do Not Recover during Therapy.
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慢性HCV，HIV和HCV/HIV共感染中循环MAIT细胞的频率降低，并且在治疗过程中不会恢复。
DOI：
10.1371/journal.pone.0159243
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Boonstra A
中科院分区：
文献类型：
--
作者：
Spaan M;Hullegie SJ;Beudeker BJ;Kreefft K;van Oord GW;Groothuismink ZM;van Tilborg M;Rijnders B;de Knegt RJ;Claassen MA;Boonstra A
粘膜相关不变T细胞（MAIT）由T细胞亚群组成，可被细菌产物和细胞因子激活以产生IFN-γ。由于对HCV感染过程中MAIT细胞的作用知之甚少，我们将其与HIV和HCV/HIV合并感染患者的表型和功能进行了比较，并确定了基于IFN-α和直接作用抗病毒治疗对HCV患者MAIT细胞的影响。采用流式细胞术检测慢性HCV （CHCV）、病毒学抑制HIV、急性HCV/HIV合并感染（AHCV/HIV）患者和健康人的血液样本MAIT和NK细胞的表型和功能。与健康人相比，CHCV、HIV和AHCV/HIV合并感染患者CD161+Vα7.2+ MAIT细胞的频率显著降低。AHCV/HIV患者MAIT细胞CD38表达升高。体外培养的MAIT细胞对IFN-α有反应，IFN-γ产生细胞的频率增加。以IFN-α为基础的CHCV治疗降低了IFN-γ+ MAIT细胞的频率，在治疗成功24周后仍观察到这种情况。重要的是，即使在基于IFN-α和不含IFN-α的CHCV治疗成功后，MAIT细胞的频率仍持续下降。我们发现，与健康个体相比，CHCV、HIV和AHCV/HIV合并感染患者血液中MAIT细胞的频率降低。CHCV的成功治疗并没有使24周随访时的MAIT细胞频率正常化。HIV和HCV感染对MAIT细胞数量和功能的影响值得进一步研究病毒感染对MAIT细胞数量和功能的影响。
Mucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Since little is known on MAIT cells during HCV infection, we compared their phenotype and function in comparison to HIV and HCV/HIV co-infected patients, and determined the effect of IFN-α-based and direct-acting antiviral therapy on MAIT cells of HCV patients. Blood samples from patients with chronic HCV (CHCV), virologically suppressed HIV, acute HCV/HIV co-infection (AHCV/HIV) and healthy individuals were examined by flowcytometry for phenotype and function of MAIT and NK cells. Compared to healthy individuals, the frequency of CD161+Vα7.2+ MAIT cells was significantly decreased in patients with CHCV, HIV and AHCV/HIV co-infection. CD38 expression on MAIT cells was increased in AHCV/HIV patients. MAIT cells were responsive to IFN-α in vitro as evidenced by enhanced frequencies of IFN-γ producing cells. IFN-α-based therapy for CHCV decreased the frequency of IFN-γ+ MAIT cells, which was still observed 24 weeks after successful therapy. Importantly, even after successful IFN-α-based as well as IFN-α-free therapy for CHCV, decreased frequencies of MAIT cells persisted. We show that the frequencies of MAIT cells are reduced in blood of patients with CHCV, HIV and in AHCV/HIV co-infection compared to healthy individuals. Successful therapy for CHCV did not normalize MAIT cell frequencies at 24 weeks follow up. The impact of HIV and HCV infection on the numbers and function of MAIT cells warrant further studies on the impact of viral infections and the antimicrobial function of MAIT cells.