The Notch signaling pathway has been recently shown to contribute to T cell differentiation in vitro. However, the in vivo function of Notch signaling in transplantation remains unknown. In this study, we investigated the importance of Delta1 in regulating the alloimmune response in vivo. Delta1 expression was upregulated on dendritic cells and monocytes/macrophages upon transplantation in a BALB/c into B6 vascularized cardiac transplant model. Whereas administration of anti-Delta1 mAb only slightly delayed survival of cardiac allografts in this fully MHC-mismatched model, it significantly prolonged graft survival in combination with single-dose CTLA4-Ig or in CD28 knockout recipients. The prolongation of allograft survival was associated with Th2 polarization and a decrease in Th1 and granzyme B-producing cytotoxic T cells. The survival benefit of Delta1 blockade was abrogated after IL-4 neutralization and in STAT6KO recipients, but was maintained in STAT4KO recipients, reinforcing the key role of Th2 cell development in its graft-prolonging effects. To our knowledge, these data demonstrate for the first time an important role of Delta1 in alloimmunity, identifying Delta1 ligand as a potential novel target for immunomodulation in transplantation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197868 | PMC |
| http://dx.doi.org/10.4049/jimmunol.1004076 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
No Association Between Donor Variables and Clinically Significant Outcomes, Reoperations, and Failure After Osteochondral Allograft Transplantation.
Am J Sports Med
January 2025
Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA.
Background: Mismatch between osteochondral allograft (OCA) donor and recipient sex has been shown to negatively affect outcomes. This study accounts for additional donor variables and clinically relevant outcomes.
Purpose: To evaluate whether donor sex, age, donor-recipient sex mismatch, and duration of graft storage affect clinical outcomes and failure rates after knee OCA transplantation.
Preservation of Liver Graft Using the Hypothermic Oxygenated Perfusion (HOPE) System: A single-center experience.
Transplant Proc
January 2025
BioBizkaia Research Health Institute, Barakaldo, Bizkaia, Spain; Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain. Electronic address:
Introduction: The hypothermic oxygenated perfusion (HOPE) system has been developed to improve the quality of previously considered suboptimal liver grafts, reduce complications, and increase the number of available donors. The aim of this study is to evaluate the results since its implementation in the liver transplant (LT) program at our center.
Materials And Methods: We conducted a retrospective descriptive analysis of all LTs with HOPE from August 2022 to November 2023 with a minimum follow-up of 3 months.
Maintenance Immunosuppression With Tacrolimus and Everolimus in Heart Transplantation Compared With the Usual Tacrolimus and Micophenolate Protocol: Results From a Retrospective Registry.
Transplant Proc
January 2025
Department of Cardiology, Advanced Heart Failure and Heart Transplant Unit, Hospital Universitario Central de Asturias, Oviedo, Spain; Health Research Institute of Asturias, ISPA, Oviedo, Spain.
Introduction: Real-life data on the long-term use of a maintenance immunosuppressive protocol in heart transplant patients using delayed Everolimus + Tacrolimus are scarce.
Methods: This is a retrospective study that included all heart transplant patients from 2011 to 2021 in two Spanish hospitals. In Hospital A, the preferred immunosuppressive strategy included Everolimus initiation at 2 months post-transplant combined with Tacrolimus and was compared with the results of Hospital B, where a standard Tacrolimus and Mycophenolate mofetil protocol was used.
Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.
Proc Natl Acad Sci U S A
January 2025
Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.
View Article and Find Full Text PDFComparative retrospective analysis of cord blood transplantation with ATG-containing conditioning regimens and haploidentical stem cell transplantation: similar survival outcomes with reduced incidence of GVHD.
Ann Med
December 2025
Department of Hematology, Peking University First Hospital, Beijing, China.
Background: Cord blood (CB) is widely used in treating haematologic disorders due to its broad availability, tolerance to significant histocompatibility antigen disparities, and low incidence of chronic graft-versus-host disease (cGVHD). The cord blood transplantation (CBT) with anti-thymocyte globulin (ATG)-containing conditioning regimens shows promise in this regard.
Methods: We conducted a retrospective review of data from patients who underwent CBT at our centre from August 2003 to December 2022.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!