{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:12:11Z","timestamp":1789567931959,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":259,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED","doi-asserted-by":"publisher","award":["JP22bk0104139"],"award-info":[{"award-number":["JP22bk0104139"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Virus-specific T cell therapy is a promising treatment for life-threatening viral infections following allogeneic hematopoietic stem cell transplantation. However, its efficacy is limited by apoptotic cell loss during in vitro expansion and the cryopreservation process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Human virus-specific T cells were expanded in vitro with interleukin-7 and interleukin-15 in RPMI 1640-based medium with or without L-arginine supplementation, and their survival, phenotype, mitochondrial function, and cytokine signaling were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Supplementation of the culture medium with L-arginine enhanced the survival of human virus-specific T cells during in vitro expansion. Supplementation of the RPMI 1640-based culture medium with L-arginine reduced apoptosis and was accompanied by increased expression of the anti-apoptotic protein MCL-1 in virus-specific CD8+ T cells. In parallel, modest differences in exhaustion- and differentiation-associated markers were observed. Consistent with these survival-associated changes, preservation of mitochondrial membrane potential was concurrently observed in non-apoptotic CD8+ T cells. Among several culture-associated factors that may contribute to mitochondrial preservation, L-arginine availability was associated, at least in part, with common gamma-chain cytokine-induced phosphorylation of mammalian target of rapamycin signalling and signal transducer and activator of transcription 5 downstream of interleukin-7 and interleukin-15 during in vitro culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings support L-arginine supplementation as a simple and clinically applicable strategy to enhance the durability of virus-specific T cell products during in vitro expansion, as well as cryopreservation and thawing.<\/jats:p>\n                  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