ArticleBlood2014
Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Successful outcomes of second hematopoietic stem cell transplantation with total nodal irradiation and ATG conditioning for graft failure in adult patients with severe aplastic anemia.Bone marrow transplantation · 2018Trial
- Combined nonmyeloablative total lymphoid irradiation and low-dose total body irradiation enhances donor chimerism and leads to islet allograft acceptance.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?Stem cell research & therapy · 2024Review
- After Bone Marrow Transplantation, the Cell-Intrinsic Th2 Pathway Promotes Recipient T Lymphocyte Survival and Regulates Graft-versus-Host Disease.ImmunoHorizons · 2023Article
- Lkb1 loss in regulatory T cells leads to dysregulation of hematopoietic stem cell expansion and differentiation in bone marrow.FEBS open bio · 2023Article
- Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance.The Journal of clinical investigation · 2021Article
- Regulation of murine NK cell exhaustion through the activation of the DNA damage repair pathway.JCI insight · 2019Article
- CD4Frontiers in immunology · 2019Review
- CXCR4 blockade improves leukemia eradication by allogeneic lymphocyte infusion.American journal of hematology · 2018Article
- Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy.Science translational medicine · 2016Article
- Regulatory T cells inhibit CD34+ cell differentiation into NK cells by blocking their proliferation.Scientific reports · 2016Article
- Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation.Frontiers in immunology · 2016Review
- Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells.Frontiers in immunology · 2016Review
- NK Cell and CD4+FoxP3+ Regulatory T Cell Based Therapies for Hematopoietic Stem Cell Engraftment.Stem cells international · 2016Review
- Regulators help new immigrants settle down?Blood · 2014Article
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Authors and funding
10 authors at 1 institution in 3 countries.
Funding
Abstract
Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique regimen that prepares recipients for allogeneic hematopoietic cell transplantation by targeting lymph nodes, while sparing large areas of the bone marrow. TLI is reported to increase the frequency of CD4(+)CD25(+)FoxP3(+) T-regulatory cells (Treg) relative to conventional T cells. In this study, barriers to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but endogenous host HSC remained. Initial donor HSC engraftment occurred only in radiation exposed marrow sites, but gradually distributed to bone marrow outside the radiation field. Sustained donor engraftment required host lymphoid cells insofar as lymphocyte deficient Rag2γc(-/-) recipients had unstable engraftment compared with wild-type. TLI/ATG treated wild-type recipients had increased proportions of Treg that were associated with increased HSC frequency and proliferation. In contrast, Rag2γc(-/-) recipients who lacked Treg did not. Adoptive transfer of Treg into Rag2γc(-/-) recipients resulted in increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby promoting the exit of host HSC from the marrow niche. Our study highlights the unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg on HSC activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.