Kared Hassen, Saeed Sahar, Klein Marina B, Shoukry Naglaa H
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada.
Department of Medicine, Divisions of Infectious Diseases/Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
PLoS One. 2014 Jul 9;9(7):e101441. doi: 10.1371/journal.pone.0101441. eCollection 2014.
Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.
丙型肝炎病毒（HCV）感染是合并感染人类免疫缺陷病毒（HIV）人群发病和死亡的主要原因。尽管α干扰素（IFN-α）对免疫系统有有害影响，但它仍然是抗HCV治疗的主要组成部分。此外，最近有研究表明IFN-α可减小潜伏HIV储存库的规模。本研究的目的是监测IFN-α在IFN治疗期间对T细胞表型以及HIV和HCV特异性T细胞增殖的影响，并确定可预测HIV/HCV合并感染患者对IFN反应的免疫标志物。我们对接受IFN-α治疗且有不同治疗结果的合并感染患者进行了T细胞数量、表型和功能的纵向分析，这些患者包括IFN-α无反应者（NR）（n = 9）和获得持续病毒学应答（SVR）的患者（n = 19）。我们检测了治疗前、治疗期间和治疗后总CD4和CD8 T细胞上激活标志物（CD38、HLA-DR）、功能标志物（CD127）和耗竭标志物（PD1、Tim-3、CD160和CD244）的表达。此外，我们检测了针对HIV-p24和HCV-NS3蛋白的HIV和HCV特异性增殖反应。在基线时，SVR患者中CD127 + CD4 T细胞的频率高于NR患者。在所有患者中，IFN-α治疗后观察到CD8 T细胞上CD127表达增加。此外，NR患者的CD8 T细胞在基线时表现出更高的耗竭状态。最后，SVR患者在基线时对HIV和HCV抗原均表现出更高的增殖反应。总体而言，SVR与基线时CD127的高表达、较低的T细胞耗竭状态以及更好的HIV和HCV增殖反应相关。这些因素可用作预测合并感染个体基于IFN治疗成功与否的非侵入性方法。
