{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:16:55Z","timestamp":1792603015463,"version":"4.5.0"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"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:p>The outcome of allogeneic hematopoietic cell transplantation (allo-HCT) largely depends on the development and management of graft-versus-host disease (GvHD), infections, and the occurrence of relapse of malignancies. Recent studies showed a lower incidence of chronic GvHD and severe acute GvHD in patients receiving naive T cell depleted grafts compared to patients receiving complete T cell depleted grafts. On the other hand, the incidence of acute GvHD in patients receiving cord blood grafts containing only naive T cells is rather low, while potent graft-versus-leukemia (GvL) responses have been observed. These data suggest the significance of naive T cells as both drivers and regulators of allogeneic reactions. The naive T cell pool was previously thought to be a quiescent, homogenous pool of antigen-inexperienced cells. However, recent studies showed important differences in phenotype, differentiation status, location, and function within the naive T cell population. Therefore, the adequate recovery of these seemingly innocent T cells might be relevant in the imminent allogeneic reactions after allo-HCT. Here, an extensive review on naive T cells and their contribution to the development of GvHD and GvL responses after allo-HCT is provided. In addition, strategies specifically directed to stimulate adequate reconstitution of naive T cells while reducing the risk of GvHD are discussed. A better understanding of the relation between naive T cells and alloreactivity after allo-HCT could provide opportunities to improve GvHD prevention, while maintaining GvL effects to lower relapse risk.<\/jats:p>","DOI":"10.3389\/fimmu.2022.893545","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:33:32Z","timestamp":1655685212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Naive T Cells in Graft Versus Host Disease and Graft Versus Leukemia: Innocent or Guilty?"],"prefix":"10.3389","volume":"13","author":[{"given":"Linde","family":"Dekker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evy","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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