The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Posttransplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression
Open accessAbstract
Post-transplantation cyclophosphamide (PTCy) recently has had a marked impact on human allogeneic hematopoietic cell transplantation (HCT). Yet, our understanding of how PTCy prevents graft-versus-host disease (GVHD) largely has been extrapolated from major histocompatibility complex (MHC)-matched murine skin allografting models that were highly contextual in their efficacy. Herein, we developed a T-cell-replete, MHC-haploidentical, murine HCT model (B6C3F1→B6D2F1) to test the putative underlying mechanisms: alloreactive T-cell elimination, alloreactive T-cell intrathymic clonal deletion, and suppressor T-cell induction. In this model and confirmed in four others, PTCy did not eliminate alloreactive T cells identified using either specific Vβs or the 2C or 4C T-cell receptors. Furthermore, the thymus was not necessary for PTCy's efficacy. Rather, PTCy induced alloreactive T-cell functional impairment which was supported by highly active suppressive mechanisms established within one day after PTCy that were sufficient to prevent new donor T cells from causing GVHD. These suppressive mechanisms included the rapid, preferential recovery of CD4+CD25+Foxp3+ regulatory T cells, including those that were alloantigen-specific, which served an increasingly critical function over time. Our results prompt a paradigm-shift in our mechanistic understanding of PTCy. These results have direct clinical implications for understanding tolerance induction and for rationally developing novel strategies to improve patient outcomes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2007) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,820
Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease
Koreth, J., Matsuoka, K.-I., Kim, H. T., McDonough, S. M., Bindra, B., Alyea, E. P., Armand, P., Cutler, C., Ho, V. T., Treister, N. S., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1108188 · Cited by 1,119
HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry
Gragert, L., Eapen, M., Williams, E., Freeman, J., Spellman, S., Baitty, R., Hartzman, R., Rizzo, J. D., Horowitz, M., Confer, D., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmsa1311707 · Cited by 1,103
Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation
Di Ianni, M., Falzetti, F., Carotti, A., Terenzi, A., Castellino, F., Bonifacio, E., Del Papa, B., Zei, T., Ostini, R. I., Cecchini, D., et al. (2011) · Blood · doi:10.1182/blood-2010-10-311894 · Cited by 1,064
Cooke, K., Kobzik, L., Martin, T., Brewer, J., Delmonte, J. J., Crawford, J., & Ferrara, J. (1996) · Blood · doi:10.1182/blood.v88.8.3230.bloodjournal8883230 · Cited by 963
Tolerance and exhaustion: defining mechanisms of T cell dysfunction
Schietinger, A., & Greenberg, P. D. (2014) · Trends in Immunology · doi:10.1016/j.it.2013.10.001 · Cited by 673
Ciurea, S. O., Zhang, M.-J., Bacigalupo, A. A., Bashey, A., Appelbaum, F. R., Aljitawi, O. S., Armand, P., Antin, J. H., Chen, J., Devine, S. M., et al. (2015) · Blood · doi:10.1182/blood-2015-04-639831 · Cited by 662
Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice
Sha, W. C., Nelson, C. A., Newberry, R. D., Kranzt, D. M., Russell, J. H., & Loh, D. Y. (1988) · Nature · doi:10.1038/335271a0 · Cited by 491
Szydlo, R., Goldman, J. M., Klein, J. P., Gale, R. P., Ash, R. C., Bach, F. H., Bradley, B. A., Casper, J. T., Flomenberg, N., Gajewski, J. L., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.5.1767 · Cited by 468
Cited by
Donor Clonal Hematopoiesis and Recipient Outcomes After Transplantation
Gibson, C. J., Kim, H. T., Zhao, L., Murdock, H. M., Hambley, B., Ogata, A., Madero-Marroquin, R., Wang, S., Green, L., Fleharty, M., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.21.02286 · Cited by 168
Van Beek, J. J. P., Puccio, S., Roberto, A., De Paoli, F., Graziano, G., Salviato, E., Alvisi, G., Zanon, V., Scarpa, A., Zaghi, E., et al. (2021) · Haematologica · doi:10.3324/haematol.2020.276352 · Cited by 6
Metadata
- Authors
- Wachsmuth, L. P., Patterson, M. T., Eckhaus, M. A., Venzon, D. J., Gress, R. E., & Kanakry, C. G.
- Venue
- Journal of Clinical Investigation
- Published
- 2019-05-06
- Volume
- 129
- Issue
- 6
- Pages
- 2357-2373
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2923738051
- Cited by
- 292
- References
- 37
- FWCI
- 18.28
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Posttransplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. https://app.cochat.ai/papers/10.1172/jci124218
- The paper
- Wachsmuth, L. P., Patterson, M. T., Eckhaus, M. A., Venzon, D. J., Gress, R. E., & Kanakry, C. G. (2019). Posttransplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. Journal of Clinical Investigation. https://doi.org/10.1172/jci124218
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
