ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2011
CD154 blockade abrogates allospecific responses and enhances CD4(+) regulatory T-cells in mouse orthotopic lung transplant.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- The role of macrophages in the mitigation by decitabine of acute allograft rejection.Frontiers in transplantation · 2025Article
- Hypomethylating therapy mitigates acute allograft rejection in a murine lung transplant model.Frontiers in transplantation · 2025Article
- IL-10 Is Critical for Regulation of Cytotoxic CD4+NKG7+ T Cells in Lung Allograft Rejection but Is Not Required for Allograft Acceptance.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome.Cells · 2022Review
- Costimulation blockade and Tregs in solid organ transplantation.Frontiers in immunology · 2022Review
- A novel model for dissecting roles of IL-17 in lung transplantation.Journal of thoracic disease · 2018Article
- Azithromycin Fails to Prevent Accelerated Airway Obliteration in T-betTransplantation proceedings · 2018Article
- Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2017Review
- Challenges and opportunities in targeting the CD28/CTLA-4 pathway in transplantation and autoimmunity.Expert opinion on biological therapy · 2017Review
- Mechanisms of graft rejection after lung transplantation.Current opinion in organ transplantation · 2017Review
- Induction of Major Histocompatibility Complex-mismatched Mouse Lung Allograft Acceptance With Combined Donor Bone Marrow: Lung Transplant Using a 12-Hour Nonmyeloablative Conditioning Regimen.Transplantation · 2016Article
- Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts.Transplantation · 2016Article
- CD8(+)IL-17(+) T Cells Mediate Neutrophilic Airway Obliteration in T-bet-Deficient Mouse Lung Allograft Recipients.American journal of respiratory cell and molecular biology · 2015Article
- Novel insights into anti-CD40/CD154 immunotherapy in transplant tolerance.Immunotherapy · 2015Review
- Lung transplantation: chronic allograft dysfunction and establishing immune tolerance.Human immunology · 2014Review
- Regulatory T cells as immunotherapy.Frontiers in immunology · 2014Review
- Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success.Journal of thoracic disease · 2012Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute cellular rejection (ACR) is a common and important clinical complication following lung transplantation. While there is a clinical need for the development of novel therapies to prevent ACR, the regulation of allospecific effector T-cells in this process remains incompletely understood. Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated the short-term role of anti-CD154 mAb therapy alone on allograft pathology and alloimmune T-cell effector responses. Untreated C57BL/6 recipients of BALB/c left lung allografts had high-grade rejection and diminished CD4(+) : CD8(+) graft ratios, marked by predominantly CD8(+) >CD4(+) IFN-γ(+) allospecific effector responses at day 10, compared to isograft controls. Anti-CD154 mAb therapy strikingly abrogated both CD8(+) and CD4(+) alloeffector responses and significantly increased lung allograft CD4(+) : CD8(+) ratios. Examination of graft CD4(+) T-cells revealed significantly increased frequencies of CD4(+) CD25(+) Foxp3(+) regulatory T-cells in the lung allografts of anti-CD154-treated mice and was associated with significant attenuation of ACR compared to untreated controls. Together, these data show that CD154/CD40 costimulation blockade alone is sufficient to abrogate allospecific effector T-cell responses and significantly shifts the lung allograft toward an environment predominated by CD4(+) T regulatory cells in association with an attenuation of ACR.
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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.