Increased expression of CD8 marker on T-cells in COVID-19 patients

Ali Ganji, Iman Farahani, Behzad Khansarinejad, Ali Ghazavi, Ghasem Mosayebi, Ali Ganji, Iman Farahani, Behzad Khansarinejad, Ali Ghazavi, Ghasem Mosayebi

Abstract

Background: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients.

Methods: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry.

Results: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05).

Conclusion: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.

Keywords: 2019-nCov; CD4 lymphocyte; CD8 lymphocyte; COVID-19; Coronavirus.

Conflict of interest statement

Declaration of competing interest The authors report no conflicts of interest.

Copyright © 2020. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Blood cells analyzing in COVID-19 infected patients. (A) WBC, (B) lymphocyte, and (C) platelet in COVID-19 infected patients compared to healthy individuals. *; P < 0.05, **; P < 0.01, ***; P < 0.001.
Fig. 2
Fig. 2
Flow cytometry analysis results. (A) Lymphocytes gating based on side and forward scatter and CD4 and CD8 counting, (B) CD8 and CD4 MFIs analysis of healthy individuals, (C) CD8 and CD4 MFIs analysis of COVID-19 infected patients.
Fig. 3
Fig. 3
Flow cytometry results. (A) CD4:CD8 count ratio, (B) CD8 MFI, and (C) CD4 MFI between COVID-19 infected patients and healthy individuals. NS; not significant; ***; P < 0.001.

References

    1. Guarner J. Oxford University Press US; 2020. Three Emerging Coronaviruses in two Decades: The Story of SARS, MERS, and now COVID-19.
    1. W.H. Organization . Vol. 3. 2020. Novel Coronavirus (2019-nCoV): Situation Report.
    1. W.H. Organization . 2020. Coronavirus Disease (COVID-2019) Situation Report; p. 51.
    1. Hu B., Zeng L.-P., Yang X.-L., Ge X.-Y., Zhang W., Li B., Xie J.-Z., Shen X.-R., Zhang Y.-Z., Wang N. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 2017;13
    1. Song H.-D., Tu C.-C., Zhang G.-W., Wang S.-Y., Zheng K., Lei L.-C., Chen Q.-X., Gao Y.-W., Zhou H.-Q., Xiang H. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. Proc. Natl. Acad. Sci. 2005;102:2430–2435.
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
    1. Jung M.-C., Pape G.R. Immunology of hepatitis B infection. Lancet Infect. Dis. 2002;2:43–50.
    1. Zaunders J., Carr A., McNally L., Penny R., Cooper D.A. Effects of primary HIV-1 infection on subsets of CD4+ and CD8+ T lymphocytes. AIDS (London, England) 1995;9:561–566.
    1. Sainz T., Lee S., Hunt P. Conference on Retroviruses and Opportunistic Infections. 2014. CMV and HIV: a double hit on the CD4/CD8 ratio.
    1. Paltrinieri S., Rossi G., Giordano A. Relationship between rate of infection and markers of inflammation/immunity in Holy Birman cats with feline coronavirus. Res. Vet. Sci. 2014;97:263–270.
    1. Diao B., Wang C., Tan Y., Chen X., Liu Y., Ning L., Chen L., Li M., Liu Y., Wang G. medRxiv; 2020. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama. 2020;323:1061–1069.
    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8:420–422.
    1. Zhang B., Zhou X., Qiu Y., Feng F., Feng J., Jia Y., Zhu H., Hu K., Liu J., Liu Z. 2020. Clinical Characteristics of 82 Death Cases With COVID-19, medRxiv.
    1. W.H. Organization . World Health Organization; 2020. Laboratory Testing for Coronavirus Disease 2019 (COVID-19) in Suspected Human Cases: Interim Guidance. 2 March 2020.
    1. Mescher M.F., Curtsinger J.M., Agarwal P., Casey K.A., Gerner M., Hammerbeck C.D., Popescu F., Xiao Z. Signals required for programming effector and memory development by CD8+ T cells. Immunol. Rev. 2006;211:81–92.
    1. Zhu J., Yamane H., Paul W.E. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 2009;28:445–489.
    1. Owen J.P., Jenni, Stranford, Kuby Sharon. Immunology. 2013;40
    1. McBride J.A., Striker R. Imbalance in the game of T cells: what can the CD4/CD8 T-cell ratio tell us about HIV and health? PLoS Pathog. 2017;13
    1. Lippi G., Plebani M., Henry B.M. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin. Chim. Acta. 2020;506:145–148.
    1. Hou J., Wan X., Shen Q., Leng Y., Xia Z., Zhao B., Zhu J., Lei S., He Y., Wu Y. 2020. Epidemiologic and Clinical Characteristics of Surgical Patients Infected With COVID-19 in Wuhan. Available at SSRN 3550044.
    1. Jason J., Inge K.L. Modulation of CD8 and CD3 by HIV or HIV antigens. Scand. J. Immunol. 2001;53:259–267.

Source: PubMed

3
Sottoscrivi