Srivastava Ruchi, Dhanushkodi Nisha, Prakash Swayam, Coulon Pierre Gregoire, Vahed Hawa, Zayou Latifa, Quadiri Afshana, BenMohamed Lbachir
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660-7913.
bioRxiv. 2022 Jul 27:2022.07.26.501655. doi: 10.1101/2022.07.26.501655.
Unvaccinated COVID-19 patients display a large spectrum of symptoms, ranging from asymptomatic to severe symptoms, the latter even causing death. Distinct Natural killer (NK) and CD4 and CD8 T cells immune responses are generated in COVID-19 patients. However, the phenotype and functional characteristics of NK cells and T-cells associated with COVID-19 pathogenesis versus protection remain to be elucidated. In this study, we compared the phenotype and function of NK cells SARS-CoV-2-specific CD4 and CD8 T cells in unvaccinated symptomatic (SYMP) and unvaccinated asymptomatic (ASYMP) COVID-19 patients. The expression of senescent CD57 marker, CD45RA/CCR7differentiation status, exhaustion PD-1 marker, activation of HLA-DR, and CD38 markers were assessed on NK and T cells from SARS-CoV-2 positive SYMP patients, ASYMP patients, and Healthy Donors (HD) using multicolor flow cytometry. We detected significant increases in the expression levels of both exhaustion and senescence markers on NK and T cells from SYMP patients compared to ASYMP patients and HD controls. In SYMP COVID-19 patients, the T cell compartment displays several alterations involving naive, central memory, effector memory, and terminally differentiated T cells. The senescence CD57 marker was highly expressed on CD8 T cells and CD8 T cells. Moreover, we detected significant increases in the levels of pro-inflammatory TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines from SYMP COVID-19 patients, compared to ASYMP COVID-19 patients and HD controls. The findings suggest exhaustion and senescence in both NK and T cell compartment is associated with severe disease in critically ill COVID-19 patients.
未接种疫苗的新冠患者表现出广泛的症状，从无症状到严重症状，后者甚至会导致死亡。新冠患者会产生不同的自然杀伤（NK）细胞以及CD4和CD8 T细胞免疫反应。然而，与新冠发病机制和保护相关的NK细胞和T细胞的表型及功能特征仍有待阐明。在本研究中，我们比较了未接种疫苗的有症状（SYMP）和无症状（ASYMP）新冠患者中NK细胞、新冠病毒特异性CD4和CD8 T细胞的表型和功能。使用多色流式细胞术评估了新冠病毒阳性SYMP患者、ASYMP患者和健康供体（HD）的NK细胞和T细胞上衰老CD57标志物的表达、CD45RA/CCR7分化状态、耗竭性PD-1标志物、HLA-DR的激活以及CD38标志物。与ASYMP患者和HD对照组相比，我们检测到SYMP患者的NK细胞和T细胞上耗竭和衰老标志物的表达水平显著增加。在有症状的新冠患者中，T细胞区室表现出几种改变，涉及幼稚、中枢记忆、效应记忆和终末分化T细胞。衰老的CD57标志物在CD8 T细胞和CD8 T细胞上高度表达。此外，与无症状新冠患者和HD对照组相比，我们检测到有症状新冠患者的促炎细胞因子TNF-α、IFN-γ、IL-6、IL-8和IL-17水平显著增加。这些发现表明，NK细胞和T细胞区室的耗竭和衰老与重症新冠患者的严重疾病有关。
