Background: Blockade of B7-CD28 interaction with CTLA4-Ig could prolong allograft survival in cardiac transplantation. NKG2D is an activating or coactivating receptor on NK cells, γδ T, and CD8 T cells and played an important role in transplant immunity.
Methods: C57BL/6 (wild type and γδ or interleukin (IL)-17) mice were transplanted with allogeneic BALB/c hearts and treated with CTLA4-Ig alone or in combination with anti-NKG2D monoclonal antibodies. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility.
Results: We found that wild type recipient treated with anti-NKG2D monoclonal antibodies plus CTLA4-Ig showed significantly prolonged survival cardiac allograft (>90 days, P<0.001). These in vivo results in combined therapy group correlated with low expression of interferon-γ whereas increased expression of IL-4 and alternatively activated macrophage markers. Furthermore, with blockade of NKG2D, the number of IL-17-producing γδ T cells was significantly reduced, which was demonstrated as the main source of IL-17 production. And in our γδ and IL-17 murine cardiac transplantation models, we found that γδ or IL-17 deficiency could significantly prolong cardiac allograft survival.
Conclusion: Blockade of NKG2D is effective in synergizing with CTLA4-Ig to promote long-term cardiac allograft survival in mice, and this effect is associated with decreased infiltration of IL-17-producing γδ T cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/TP.0b013e31823ffce7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
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.
Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies.
Br J Anaesth
January 2025
Population Health Research Institute, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
Background: Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery.
Methods: In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models.
The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.
View Article and Find Full Text PDFMitochondrial 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 PDFHomozygous Familial Hypercholesterolemia Treatment: New Developments.
Curr Atheroscler Rep
January 2025
Carbohydrate and Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Purpose Of Review: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH.
Recent Findings: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function.
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!