SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine

Sudhir Gupta; Sudhanshu Agrawal; Ashley Sandoval; Houfen Su; Michelle Tran; Yesim Demirdag

doi:10.1007/s10875-022-01256-y

SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine

J Clin Immunol. 2022 Jul;42(5):914-922. doi: 10.1007/s10875-022-01256-y. Epub 2022 Apr 2.

Authors

Sudhir Gupta¹, Sudhanshu Agrawal², Ashley Sandoval², Houfen Su², Michelle Tran², Yesim Demirdag²

Affiliations

¹ Division of Basic and Clinical Immunology, Medical Sciences C, University of California, Irvine, CA, C-24092697, USA. sgupta@uci.edu.
² Division of Basic and Clinical Immunology, Medical Sciences C, University of California, Irvine, CA, C-24092697, USA.

Abstract

Purpose: CD8 cytotoxic T cells (CTLs) play a critical role in the clearance of virally infected cells. SARS-CoV-2-specific CD8 T cells and functional CTLs in natural infections and following COVID-19 vaccine in primary antibody deficiency (PAD) have not been reported. In this study, we evaluated T cell response following COVID-19 or COVID-19 mRNA vaccination in patients with PADs by assessing SARS-CoV-2 tetramer-positive CD8 T cells and functional CTLs.

Methods: SARS-CoV-2-specific CD8 and functional CTLs were examined in a patient with X-linked agammaglobulinemia (XLA) and a patient with common variable immunodeficiency (CVID) following COVID-19 infection, and in 5 patients with CVID and 5 healthy controls 1 month following 2nd dose of COVID-19 mRNA vaccine (Pfizer-BioNTech). Cells were stained with SARS-CoV-2 spike protein-specific tetramers, and for functional CTLs (CD8⁺ CD107a⁺ granzyme B⁺ perforin⁺), with monoclonal antibodies and isotype controls and analyzed by flow cytometry.

Results: SARS-CoV-2-specific tetramer + CD8 T cells and functional CTLs in the patient with XLA following COVID-19 infection were higher, as compared to healthy control subject following COVID-19 infection. On the other hand, SARS-CoV2-tetramer + CD8 T cells and functional CTLs were lower in CVID patient following COVID19 infection as compared to healthy control following COVID-19 infection. SARS-CoV2-tetramer + CD8 T cells and functional CTLs were significantly lower in SARS-CoV2-naive CVID patients (n = 10) following vaccination when compared to SARS-CoV-2-naive healthy vaccinated controls (n = 10).

Conclusions: CVID is associated with reduced SARS-CoV-2-specific CD8 T cells and functional CTLs in both natural SARS-CoV-2 infection and in response to SARS-CoV-2 mRNA vaccine, whereas natural infection in XLA is associated with a robust SARS-CoV-2-specific CD8 and functional CTL responses.

Keywords: CTLs; CVID; Pfizer/BNT vaccine; SARS-CoV-2-specific CD8 T cells; XLA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
BNT162 Vaccine
CD8-Positive T-Lymphocytes* / immunology
COVID-19 Vaccines* / immunology
COVID-19* / prevention & control
Humans
Immunologic Memory
Primary Immunodeficiency Diseases* / immunology
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Substances

Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
BNT162 Vaccine

Grants and funding

UL1 TR001414/TR/NCATS NIH HHS/United States