ArticleTransplantation2016
mTOR Inhibition Suppresses Posttransplant Alloantibody Production Through Direct Inhibition of Alloprimed B Cells and Sparing of CD8+ Antibody-Suppressing T cells.
Article in Transplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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.
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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
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Impact of rapamycin on delayed graft function in kidney transplant recipients: a meta-analysis.Renal failure · 2025Pooled it
- Pooled it
- Passenger Lymphocyte Syndrome With Multiple Allo- and Autoantibodies Following Liver Transplantation: A Case Report.Case reports in transplantation · 2026Article
- Impact of immunosuppressants on tumor pulmonary metastasis: new insight into transplantation for hepatocellular carcinoma.Cancer biology & medicine · 2024Review
- Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy.Journal of clinical medicine · 2023Article
- Impact of everolimus plus calcineurin inhibitor on formation of non-HLA antibodies and graft outcomes in kidney transplant recipients: 12-month results from the ATHENA substudy.Frontiers in transplantation · 2023Article
- Antibody-suppressor CXCR5American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- B cell reconstitution following alemtuzumab induction under a belatacept-based maintenance regimen.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Rapamycin attenuates Tc1 and Tc17 cell responses in cigarette smoke-induced emphysema in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- Antibody-suppressor CD8+ T Cells Require CXCR5.Transplantation · 2019Article
- Apoptotic cell-based therapies for promoting transplantation tolerance.Current opinion in organ transplantation · 2018Review
- Activation of the mTOR signaling pathway is required for asthma onset.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundDe novo alloantibodies (donor-specific antibody) contribute to antibody-mediated rejection and poor long-term graft survival. Because the development of donor-specific antibody is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi), and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity.
methodsWild-type or CD8-depleted mice were transplanted with allogeneic hepatocytes. Recipients were treated with mTORi and/or CNi and serially monitored for alloantibody and graft survival. The direct effect of mTORi and CNi on alloprimed B cell function was investigated in Rag1 mice adoptively transferred with alloprimed IgG1 B cells. The efficacy of mTORi and/or CNi to suppress CD8-mediated cytotoxicity of IgG1 B cells was evaluated in in vitro and in vivo cytotoxicity assays.
resultsMammalian target of rapamycin inhibitors, but not CNi, reduced alloantibody production in transplant recipients, directly suppressed alloantibody production by alloprimed IgG1 B cells and delayed graft rejection in both low and high alloantibody producers. Combination treatment with mTORi and CNi resulted in loss of the inhibitory effect observed for mTORi monotherapy in part due to CNi suppression of CD8 T cells which downregulate alloantibody production (CD8 TAb-supp cells).
conclusionsOur data support that mTORi is a potent inhibitor of humoral immunity through suppression of alloprimed B cells and preservation of CD8 TAb-supp cells. In contrast, alloantibody is readily detected in CNi-treated recipients because CNi does not suppress alloprimed B cells and interferes with downregulatory CD8 TAb-supp cells.
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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.