MiCAN Technologies Inc., KKVP 1-36, Goryo-Ohara, Nishikyo-Ku, Kyoto, 615-8245, Japan.
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2024 Nov 4;14(1):26660. doi: 10.1038/s41598-024-77969-4.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit both T cell and B cell immune responses in immunocompetent individuals. However, the mechanisms underlying the antiviral effects mediated by CD4 T cells are not fully understood. In this study, we analyzed the culture supernatant (SN) from polyclonally stimulated human CD4 T cells as a model for soluble mediators derived from SARS-CoV-2-stimulated CD4 T cells. Interestingly, this SN inhibited SARS-CoV-2 propagation in a viral strain- and host cell type-dependent manner. The original wild-type showed the highest susceptibility, whereas the Delta variant exhibited resistance in the human monocyte cell line. In addition, antibody-dependent enhancement (ADE) of infection with the original strain was also abolished in the presence of the SN. The findings showed that the inhibitory effect on viral propagation by the SN was mostly attributed to interferon-γ (IFN-γ) that was present in the SN. These results highlight the potential role of IFN-γ as an anti-SARS-CoV-2 mediator derived from CD4 T cells, and suggest that we need to understand the SARS-CoV-2 strain-dependent sensitivity to IFN-γ in controlling clinical outcomes. In addition, characterization of new SARS-CoV-2 variants in terms of IFN-γ-sensitivity will have important implications for selecting therapeutic strategies.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染和疫苗接种会在免疫功能正常的个体中引起 T 细胞和 B 细胞免疫反应。然而，CD4 T 细胞介导的抗病毒作用的机制尚不完全清楚。在这项研究中，我们分析了经多克隆刺激的人 CD4 T 细胞的培养上清液（SN），作为源自 SARS-CoV-2 刺激的 CD4 T 细胞的可溶性介质的模型。有趣的是，这种 SN 以依赖病毒株和宿主细胞类型的方式抑制 SARS-CoV-2 的增殖。原始野生型对 SN 的敏感性最高，而 Delta 变体在人单核细胞系中则具有抗性。此外，在 SN 存在的情况下，感染原株的抗体依赖性增强（ADE）也被消除。研究结果表明，SN 对病毒增殖的抑制作用主要归因于存在于 SN 中的干扰素-γ（IFN-γ）。这些结果突出了 IFN-γ作为源自 CD4 T 细胞的抗 SARS-CoV-2 介质的潜在作用，并表明我们需要了解 IFN-γ对控制临床结果的 SARS-CoV-2 株敏感性。此外，对 IFN-γ敏感性的新 SARS-CoV-2 变体进行特征描述，对于选择治疗策略具有重要意义。
