Spaan Michelle, Hullegie Sebastiaan J, Beudeker Boris J B, Kreefft Kim, van Oord Gertine W, Groothuismink Zwier M A, van Tilborg Marjolein, Rijnders Bart, de Knegt Robert J, Claassen Mark A A, Boonstra Andre
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Infectious Diseases section Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
PLoS One. 2016 Jul 14;11(7):e0159243. doi: 10.1371/journal.pone.0159243. eCollection 2016.
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.
黏膜相关恒定T（MAIT）细胞是T细胞的一个亚群，可被细菌产物和细胞因子激活以产生干扰素-γ。由于丙型肝炎病毒（HCV）感染期间对MAIT细胞了解甚少，我们将其表型和功能与HIV及HCV/HIV合并感染患者进行了比较，并确定了基于干扰素-α的治疗和直接抗病毒治疗对HCV患者MAIT细胞的影响。
通过流式细胞术检测慢性HCV（CHCV）患者、病毒学抑制的HIV患者、急性HCV/HIV合并感染（AHCV/HIV）患者及健康个体的血样，以分析MAIT细胞和自然杀伤（NK）细胞的表型和功能。
与健康个体相比，CHCV患者、HIV患者及AHCV/HIV合并感染患者中CD161+Vα7.2+ MAIT细胞的频率显著降低。AHCV/HIV患者MAIT细胞上CD38的表达增加。体外实验表明MAIT细胞对干扰素-α有反应，产生干扰素-γ的细胞频率增加证明了这一点。基于干扰素-α的HCV治疗降低了产生干扰素-γ的MAIT细胞频率，在成功治疗24周后仍可观察到这一现象。重要的是，即使在基于干扰素-α的HCV治疗以及无干扰素治疗成功后，MAIT细胞频率仍持续降低。我们发现，与健康个体相比，CHCV患者、HIV患者及AHCV/HIV合并感染患者血液中MAIT细胞的频率降低。HCV成功治疗后24周随访时，MAIT细胞频率未恢复正常。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的影响以及MAIT细胞的抗菌功能。
