ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2021
In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Belatacept and regulatory T cells in transplantation: synergistic strategies for immune tolerance and graft survival.Clinical transplantation and research · 2024Review
- Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling.Cell reports · 2024Article
- IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice.Nature communications · 2024Article
- Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients.Frontiers in transplantation · 2024Review
- Treg Therapy for the Induction of Immune Tolerance in Transplantation-Not Lost in Translation?International journal of molecular sciences · 2023Review
- Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics.Clinical immunology (Orlando, Fla.) · 2023Review
- Tregs in transplantation tolerance: role and therapeutic potential.Frontiers in transplantation · 2023Review
- Oral alloantigen exposure promotes donor-specific tolerance in a mouse model of minor-mismatched skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Chronic CD40L blockade is required for long-term cardiac allograft survival with a clinically relevant CTLA4-Ig dosing regimen.Frontiers in immunology · 2022Article
- Costimulation blockade and Tregs in solid organ transplantation.Frontiers in immunology · 2022Review
- In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CTLA4Ig has been shown to improve kidney allograft function, but an increased frequency of early rejection episodes poses a major obstacle for more widespread clinical use. The deleterious effect of CTLA4Ig on Treg numbers provides a possible explanation for graft injury. Therefore, we aimed at improving CTLA4Ig's efficacy by therapeutically increasing the number of Tregs. Murine cardiac allograft transplantation (BALB/c to B6) was performed under CTLA4Ig therapy modeled after the clinically approved dosing regimen and Tregs were transferred early or late after transplant. Neither early nor late Treg transfer prolonged allograft survival. Transferred Tregs were traceable in various lymphoid compartments but only modestly increased overall Treg numbers. Next, we augmented Treg numbers in vivo by means of IL2 complexes. A short course of IL2/anti-IL2-complexes administered before transplantation reversed the CTLA4Ig-mediated decline in Tregs. Of note, the addition of IL2/anti-IL2-complexes to CTLA4Ig therapy substantially prolonged heart allograft survival and significantly improved graft histology on day 100. The depletion of Tregs abrogated this effect and resulted in a significantly diminished allograft survival. The increase in Treg numbers upon IL2 treatment was associated with a decreased expression of B7 on dendritic cells. These results demonstrate that therapy with IL2 complexes improves the efficacy of CTLA4Ig by counterbalancing its unfavorable effect on Tregs.
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