ArticleTransplantation2013
Inhibitory effects of belatacept on allospecific regulatory T-cell generation in humans.
Article in Transplantation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Combination antagonism of TNF superfamily signaling for T cell immunosuppression.Frontiers in immunology · 2026Article
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- Belatacept and regulatory T cells in transplantation: synergistic strategies for immune tolerance and graft survival.Clinical transplantation and research · 2024Review
- Immune-checkpoint expression in antigen-presenting cells (APCs) of cytomegaloviruses infection after transplantation: as a diagnostic biomarker.Archives of microbiology · 2023Review
- Psoriasis in the transplant population.Archives of dermatological research · 2023Review
- Tregs in transplantation tolerance: role and therapeutic potential.Frontiers in transplantation · 2023Review
- Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Review
- ACTH treatment promotes murine cardiac allograft acceptance.JCI insight · 2021Article
- Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells.Frontiers in immunology · 2021Review
- Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study.Transplantation direct · 2020Article
- The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens.International journal of molecular sciences · 2020Review
- Impact of infection on transplantation tolerance.Immunological reviews · 2019Review
- Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts.Brain : a journal of neurology · 2019Article
- Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.Advances in cancer research · 2019Review
- Ex Vivo Generation of Donor Antigen-Specific Immunomodulatory Cells: A Comparison Study of Anti-CD80/86 mAbs and CTLA4-lg Costimulatory Blockade.Cell transplantation · 2018Article
- Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection.Biomaterials · 2018Article
- CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates.The Journal of clinical investigation · 2018Article
- Belatacept and Autoimmune Adverse Events.Transplantation · 2018Article
- A Phase I Clinical Trial with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants.Scientific reports · 2018Article
- Updated follow-up of a tolerance protocol in HLA-identical renal transplant pairs given donor hematopoietic stem cells.Human immunology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIt is unclear if new costimulatory blockade agents, such as the cytotoxic T lymphocyte-associated antigen 4-Ig molecule belatacept (BEL), promote or inhibit the potential for immunologic tolerance in transplantation. We therefore tested the in vitro effects of BEL on human regulatory T cells (Tregs) in mixed lymphocyte reactions (MLR) alone and in combination with maintenance agents used in transplant recipients.
methodsBEL, mycophenolic acid (MPA), and sirolimus, either alone or in combination, were added to healthy volunteer Treg-MLR, testing (a) H-TdR incorporation for inhibition of lymphoproliferation and (b) flow cytometry to analyze for newly generated CD4+ CD25(high) FOXP3+ Tregs in carboxyfluorescein succinimidyl ester-labeled MLR responders. In addition, the modulatory effects of putative Tregs generated in the presence of these drugs were also tested using the lymphoproliferation and flow cytometric assays.
resultsIn comparison with medium controls, BEL dose-dependently inhibited both lymphoproliferation and Treg generation in human leukocyte antigen DR matched and mismatched MLRs either alone or in combination with MPA or sirolimus. However, MPA alone inhibited lymphoproliferation but significantly enhanced Treg generation at subtherapeutic concentrations (P<0.01). In addition, purified CD4+ CD127- cells generated in MLR in the presence of MPA and added as third component modulators in fresh MLRs significantly enhanced newly developed Tregs in the proliferating responder cells compared with those generated with BEL or medium controls.
conclusionsBEL alone and in combination with agents used in transplant recipients inhibits the in vitro generation of human Tregs. BEL might therefore be a less optimal agent for tolerance induction in human organ transplantation.
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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.