Development of potent HLA-A02:01-restricted peptide-based cytotoxic T-cells against SARS-CoV-2 infections in patients awaiting a kidney transplant

Controlling viral infections prior to solid organ transplantation is vital for successful engraftment and overall well-being of patients. One promising approach involves the deployment of viral antigen-specific cytotoxic T cells to eradicate viral pathogens. Although there have been attempts to deve...

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Published in:Frontiers in immunology Vol. 16; p. 1664371
Main Authors: Chang, Chih-Chao, Liu, Ya Nan, Xu, Zheng, Vasilescu, Elena-Rodica, Li, Ping, Ho, Eric K., Li, Muyang, Husain, Syed A., Bhagat, Govind, Mohan, Sumit, Vlad, George, Suciu-Foca, Nicole
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 2025
Subjects:
Adult
Aged
CD8-Positive T-Lymphocytes - immunology
cell-mediated immunity
COVID-19
COVID-19 - immunology
COVID-19 - therapy
Female
HLA-A2 Antigen - immunology
Humans
Kidney Transplantation
Male
Middle Aged
organ transplant
Peptides - immunology
SARS-CoV-2
SARS-CoV-2 - immunology
Spike Glycoprotein, Coronavirus - immunology
T-cell therapy
T-Lymphocytes, Cytotoxic - immunology
tetramer
COVID-19
SARS-CoV-2
immunophenotyping
organ transplant
antigen specific-cytotoxic T cells
tetramer
T-cell therapy
cell-mediated immunity
ISSN:1664-3224, 1664-3224
Online Access:Get full text
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Summary:Controlling viral infections prior to solid organ transplantation is vital for successful engraftment and overall well-being of patients. One promising approach involves the deployment of viral antigen-specific cytotoxic T cells to eradicate viral pathogens. Although there have been attempts to develop anti-viral vaccines in the literature, the limited number of virus-specific cells which can be generated in the autologous system make it impracticable for autologous therapy. We developed a straightforward and scalable method for the expansion of SARS-CoV-2 Spike S1 peptide-specific cytotoxic CD8 T cells. This was achieved through combinatorial stimulation with S peptide-conjugated polystyrene microspheres in the presence of cytokines IL-2, IL-7, and IL-15 for 14 days. Using A2/S -specific tetramers as markers, we compared induction of S-specific CD8 T cells from patients awaiting kidney transplantation (n=67) with that of normal controls (n=65). We found that this method has the potential to achieve at least a 10-fold up to 200-fold increase in S-specific CD8 T cells in 34.3% of kidney transplant candidates and 36.9% of normal controls, respectively. These SARS-CoV-2 specific CD8 T cells released inflammatory cytokines, expressed effector-memory T cells markers, and killed target cells in a dose-dependent and antigen-specific manner. Our study demonstrates that viral antigen-specific cytotoxic CD8 T cells can be robustly enriched from peripheral blood mononuclear cells of both healthy individuals and patients with kidney diseases using peptide-conjugated microspheres. Our findings provide novel insights into a potential therapeutic approach, using autologous anti-viral CD8 T cells for transplant recipients/candidates.
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ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2025.1664371