{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:53:16Z","timestamp":1790833996871,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In the complex interplay between inflammation and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-HSCT), viral reactivations are often observed and cause substantial morbidity and mortality. As toxicity after allo-HSCT within the context of viral reactivations is mainly driven by \u03b1\u03b2 T cells, we describe that by delaying \u03b1\u03b2 T cell reconstitution through defined transplantation techniques, we can harvest the full potential of early reconstituting \u03b3\u03b4 T cells to control viral reactivations. We summarize evidence of how the \u03b3\u03b4 T cell repertoire is shaped by CMV and EBV reactivations after allo-HSCT, and their potential role in controlling the most important, but not all, viral reactivations. As most \u03b3\u03b4 T cells recognize their targets in an MHC-independent manner, \u03b3\u03b4 T cells not only have the potential to control viral reactivations but also to impact the underlying hematological malignancies. We also highlight the recently re-discovered ability to recognize classical HLA-molecules through a \u03b3\u03b4 T cell receptor, which also surprisingly do not associate with GVHD. Finally, we discuss the therapeutic potential of \u03b3\u03b4 T cells and their receptors within and outside the context of allo-HSCT, as well as the opportunities and challenges for developers and for payers.<\/jats:p>","DOI":"10.3390\/v14010117","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T22:03:13Z","timestamp":1641852193000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of \u03b3\u03b4 T Cells as a Line of Defense in Viral Infections after Allogeneic Stem Cell Transplantation: Opportunities and Challenges"],"prefix":"10.3390","volume":"14","author":[{"given":"Anke","family":"Janssen","sequence":"first","affiliation":[{"name":"Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"van Diest","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vyborova","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenneke","family":"Schrier","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Princess Maxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Bruns","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Sebestyen","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy","family":"Straetemans","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moniek","family":"de Witte","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-7806","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Kuball","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e580","DOI":"10.1097\/HS9.0000000000000580","article-title":"Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust","volume":"5","author":"Daenen","year":"2021","journal-title":"Hemasphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1200\/JCO.20.00150","article-title":"Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study","volume":"38","author":"Chang","year":"2020","journal-title":"J. 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