Awad Gounwa, Roch Toralf, Stervbo Ulrik, Kaliszczyk Sviatlana, Stittrich Anna, Hörstrup Jan, Cinkilic Ocan, Appel Heiner, Natrus Larysa, Gayova Ludmila, Seibert Felix, Bauer Frederic, Westhoff Timm, Nienen Mikalai, Babel Nina
University Hospital Marien Hospital Herne, Ruhr-University of Bochum, Bochum, Germany.
BIH Center for Regenerative Therapies, Charité - University Medicine Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany.
Mol Ther Methods Clin Dev. 2021 Mar 23;21:288-298. doi: 10.1016/j.omtm.2021.03.012. eCollection 2021 Jun 11.
While virus-specific antibodies are broadly recognized as correlates of protection, virus-specific T cells are important for direct clearance of infected cells. Failure to generate hepatitis B virus (HBV)-specific antibodies is well-known in patients with end-stage renal disease. However, whether and to what extent HBV-specific cellular immunity is altered in this population and how it influences humoral immunity is not clear. To address it, we analyzed HBV-reactive T cells and antibodies in hemodialysis patients post vaccination. 29 hemodialysis patients and 10 healthy controls were enrolled in a cross-sectional study. Using multiparameter flow cytometry, HBV-reactive T cells were analyzed and functionally dissected based on granzyme B, interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and IL-4 expression. Importantly, HBV-reactive CD4 T cells were detected not only in all patients with sufficient titers but also in 70% of non-responders. Furthermore, a correlation between the magnitude of HBV-reactive CD4 T cells and post-vaccination titers was observed. In summary, our data showed that HBV-reactive polyfunctional T cells were present in the majority of hemodialysis patients even if humoral immunity failed. Further studies are required to confirm their antiviral capacity. The ability to induce vaccine-reactive T cells paves new ways for improved vaccination and therapy protocols.
虽然病毒特异性抗体被广泛认为是保护的相关因素，但病毒特异性T细胞对于直接清除受感染细胞很重要。在终末期肾病患者中，无法产生乙型肝炎病毒（HBV）特异性抗体是众所周知的。然而，该人群中HBV特异性细胞免疫是否改变以及改变的程度如何，以及它如何影响体液免疫尚不清楚。为了解决这个问题，我们分析了血液透析患者接种疫苗后的HBV反应性T细胞和抗体。29名血液透析患者和10名健康对照者参与了一项横断面研究。使用多参数流式细胞术，基于颗粒酶B、干扰素-γ（IFN-γ）、肿瘤坏死因子α（TNF-α）、白细胞介素-2（IL-2）和IL-4的表达，对HBV反应性T细胞进行了分析和功能剖析。重要的是，不仅在所有抗体滴度足够的患者中检测到了HBV反应性CD4 T细胞，而且在70%的无反应者中也检测到了。此外，还观察到HBV反应性CD4 T细胞的数量与接种疫苗后的抗体滴度之间存在相关性。总之，我们的数据表明，即使体液免疫失败，大多数血液透析患者中仍存在HBV反应性多功能T细胞。需要进一步研究来证实它们的抗病毒能力。诱导疫苗反应性T细胞的能力为改进疫苗接种和治疗方案开辟了新途径。
