{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:13:25Z","timestamp":1759796005829,"version":"build-2065373602"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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 <jats:italic>in vitro<\/jats:italic> in the autologous system make it impracticable for autologous therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a straightforward and scalable method for the <jats:italic>in vitro<\/jats:italic> expansion of SARS-CoV-2 Spike S1 peptide-specific cytotoxic CD8<jats:sup>+<\/jats:sup> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using A2\/S<jats:sub>269<\/jats:sub>-specific tetramers as markers, we compared induction of S-specific CD8<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells in 34.3% of kidney transplant candidates and 36.9% of normal controls, respectively. These SARS-CoV-2 specific CD8<jats:sup>+<\/jats:sup> T cells released inflammatory cytokines, expressed effector-memory T cells markers, and killed target cells in a dose-dependent and antigen-specific manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates that viral antigen-specific cytotoxic CD8<jats:sup>+<\/jats:sup> T cells can be robustly enriched <jats:italic>in vitro<\/jats:italic> 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<jats:sup>+<\/jats:sup> T cells for transplant recipients\/candidates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1664371","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:21:36Z","timestamp":1759728096000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of potent HLA-A02:01-restricted peptide-based cytotoxic T-cells against SARS-CoV-2 infections in patients awaiting a kidney transplant"],"prefix":"10.3389","volume":"16","author":[{"given":"Chih-Chao","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya Nan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena-Rodica","family":"Vasilescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric K.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed A.","family":"Husain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Govind","family":"Bhagat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Vlad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Suciu-Foca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"B1","unstructured":"COVID-19 breakthrough data\n          \n          \n            \n              State\n              NY\n            \n          \n          \n          2023"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1204831","article-title":"Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1259","DOI":"10.1002\/iid3.1259","article-title":"Immunocompromised individuals are at increased risk of COVID-19 breakthrough infection, hospitalization, and death in the post-vaccination era: A systematic review","volume":"12","author":"Bytyci","year":"2024","journal-title":"Immun Inflammation Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.immuni.2023.02.017","article-title":"SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses","volume":"56","author":"Koutsakos","year":"2023","journal-title":"Immunity"},{"key":"B5","doi-asserted-by":"publisher","first-page":"108728","DOI":"10.1016\/j.celrep.2021.108728","article-title":"Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients","volume":"34","author":"Tan","year":"2021","journal-title":"Cell Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.jaci.2020.04.013","article-title":"A possible role for B cells in COVID-19? 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