ArticleNature communications2022
Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 18 citations in OpenAlex.
- Single-cell analysis of skin and blood reveals systemic immune responses to ultraviolet B and their impairment in MS.Journal of neuroinflammation · 2026Trial
- IL-2 mutein promotes antigen-specific transplant acceptance in mice through expansion of ST2Nature communications · 2026Article
- Costimulation loss enhances IL-2-driven Treg generation by PI3K-STAT3 inhibition in CNS autoimmunity.EMBO molecular medicine · 2026Article
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.Molecular cancer · 2024Review
- IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice.Nature communications · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Regulatory T Cells for Control of Autoimmunity.Advances in experimental medicine and biology · 2024Article
- The effect of abatacept on T-cell activation is not long-livedDiscovery immunology · 2024Article
- Regulatory T cells in autoimmune kidney diseases and transplantation.Nature reviews. Nephrology · 2023Review
- Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.Molecular cancer · 2023Review
- Development and function of FOXP3+ regulators of immune responses.Clinical and experimental immunology · 2023Article
- Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant.Science advances · 2023Article
- Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective.Immunotherapy advances · 2023Review
- Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.Frontiers in endocrinology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.
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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.