key: cord-0697559-3hsn6svq authors: Lei, Lei; Qian, Hongbo; Yang, Xiaofang; Zhang, Xingzhe; Zhang, Dan; Dai, Tongxin; Guo, Rui; Shi, Lin; Cheng, Yanbin; Zhang, Baojun; Zhou, Xiaobo; Hu, Jinsong; Guo, Yaling title: The phenotypic changes of γδ T cells in COVID‐19 patients date: 2020-08-30 journal: J Cell Mol Med DOI: 10.1111/jcmm.15620 sha: 3faa6821f87485a8f87590178fdfe6f4db354ff0 doc_id: 697559 cord_uid: 3hsn6svq A novel pneumonia‐associated respiratory syndrome named coronavirus disease‐2019 (COVID‐19), which was caused by SARS‐CoV‐2，broke out in Wuhan, China, in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS‐CoV‐2 infections. The information regarding the immunological characteristics in COVID‐19 patients remains limited. Here, we collected the blood samples from 18 healthy donors (HD) and 38 COVID‐19 patients to analyze changes on γδ T cell population. In comparison with HD, the γδ T cell percentage decreased, while the activation marker CD25 expression increased in response to SARS‐CoV‐2 infection. Interestingly, the CD4 expression was upregulated in γδ T cells reflecting the occurrence of a specific effector cell population, which may serve as a biomarker for the assessment of SARS‐CoV‐2 infection. A severe pneumonia-associated respiratory syndrome spread rapidly in Wuhan, China, at the end of 2019. A novel coronavirus, officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of emerging cases of severe pneumonia. 1, 2, 3 Officially named by WHO, the coronavirus infection disease-19 (COVID- 19) outbreak was listed as a public health emergency of international concern. The virus has so far caused 81 896 confirmed cases and 3287 deaths in China according to WHO by 8 April 2020. COVID-19 has rapidly spread in more than 180 countries worldwide, including Italy, Iran, Japan and the United States. SARS-CoV-2 is an enveloped positive-sense RNA virus, which belongs to the family of coronaviruses including SARS-CoV and MERS-CoV. 4, 5 Currently, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. Clinical treatments for COVID-19 patients are primarily supportive and symptomatic treatments. There are several existing antiviral agents that can be repurposed to develop effective interventions against this novel coronavirus. 6 However, toxicology studies and clinical trials are required for potential uses in the clinic. According to the pathological reports for COVID-19, SARS-CoV-2 mainly caused inflammatory responses in the lungs. 7 Several studies showed that COVID-19 patients developed lymphopenia and rising pro-inflammatory cytokines in severe cases. 8, 9 Inflammation can be triggered when innate and adaptive immune cells detect SARS-CoV-2 infection. Innate T cells can provide a first line of defence against pathogens. However, how innate T cells respond to SARS-COV-2 infection remains unclear. Among innate immune cells, γδ T cells proliferate rapidly and respond to pathogens by inducing apoptosis, mediating antigen presentation and immune regulation. 10 In healthy adult humans, γδ T cells represent 1%-10% of total circulating lymphocytes, predominately displaying the CD4 and CD8 double-negative phenotype. 11 However, in some cases, a fraction of γδ T cells can express either CD4 or CD8. [12] [13] [14] The γδ T cells in Itk-and Id3-deficient mice exhibited an increase in CD4 and CD44 expression, as well as cytokine production (IL-4, IFNγ or IL-17), indicating an enhanced effector function in the context of infection or disease occurrence. 15,16 γδ T cells do not recognize classical peptide antigens, their TCRs are non-MHC restricted, and they can respond to pathogen-associated molecular patterns and produce cytokines in the absence of TCR ligands. 17 Furthermore, γδ T cells can defend against viral infection by secreting IFNγ and upregulating the expression of NKG2D, perforin, granzyme B and FasL, etc 18, 19 In many infections, the number of γδ T cells increases both locally and systemically a few days post-infection. A study found that the ratio of γδ T cells among total lymphocytes in the lungs significantly increased in mice infected with influenza A (H1N1) virus 3 days following infection. 19 This observation suggests that γδ T cells play an important role in the host immune response. During acute HIV infection, previous studies showed that the expression of the activation marker, CD25, is significantly increased on γδ T cells, 14 The study included 18 healthy controls and 40 patients from February 18 to March 4. In the HD group, the median age is 39.06 ± 4.26 years, with equal numbers of male and female subjects. The median age of the patient group was 45.08 ± 4.06 years, including 23 male patients (60.53%) and 15 female patients (39.47%). The 38 patients enrolled were all confirmed to have SARS-CoV-2 infection using PCR tests on throat swab specimens. All patients were categorized as mild by clinical manifestations. Student's t test was performed for two group analysis using GraphPad Prism 7.0 software. * and ** stands for P < .05 and P < .01, respectively. This work was supported in part by grants from a COVID-19 special project from Xi'an Jiaotong University Foundation (xzy032020002). We thank all the doctors, nurses, public health workers and patients for their contribution against SARS-CoV-2 infection. We declare no competing interests. The data sets used and analysed in the current study are available from the corresponding author upon reasonable request. https://orcid.org/0000-0002-7506-2180 Jinsong Hu https://orcid.org/0000-0003-0565-4567 A novel coronavirus outbreak of global health concern A pneumonia outbreak associated with a new coronavirus of probable bat origin A Novel Coronavirus from patients with pneumonia in China Return of the Coronavirus: 2019-nCoV Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Baricitinib as potential treatment for 2019-nCoV acute respiratory disease Pathological findings of COVID-19 associated with acute respiratory distress syndrome A new coronavirus associated with human respiratory disease in China Clinical features of patients infected with 2019 novel coronavirus in Wuhan The role of Vdelta2-negative gammadelta T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation The function of gammadelta T cells in innate immunity Human Peripheral CD4(+) Vdelta1(+) gammadeltaT Cells Can Develop into alphabetaT Cells Characterization of immune modulating functions of gammadelta T cell subsets in a gnotobiotic pig model of human rotavirus infection Activation of γδT cells by influenza virus and its cytotoxic effects Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production Id3 Restricts gammadelta NKT cell expansion by controlling Egr2 and c-Myc activity The molecular basis of TCR germline bias for MHC is surprisingly simple Human Vgamma9Vdelta2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells Vgamma4(+)gammadeltaT cells aggravate severe H1N1 influenza virus infection-induced acute pulmonary immunopathological injury via secreting interleukin-17A Distortion of memory Vdelta2 gammadelta T cells contributes to immune dysfunction in chronic HIV infection gammadelta T cells are involved in acute HIV infection and associated with AIDS progression gammadelta T lymphocytes: an effector cell in autoimmunity and infection gammadelta T cells link innate and adaptive immune responses