ArticleProceedings of the National Academy of Sciences of the United States of America2012
Proapoptotic protein Bim is differentially required during thymic clonal deletion to ubiquitous versus tissue-restricted antigens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Multifaceted regulation of thymic tolerance by pattern recognition cascades.Frontiers in immunology · 2026Review
- Basic interactions responsible for thymus function explain the convoluted medulla shape.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.Nature communications · 2025Article
- Targeting the TNF/IAP pathway synergizes with anti-CD3 immunotherapy in T-cell acute lymphoblastic leukemia.Blood · 2024Article
- Rare copy number variation in autoimmune Addison's disease.Frontiers in immunology · 2024Article
- The Adaptation Model of Immunity: Signal IV Matters Most in Determining the Functional Outcomes of Immune Responses.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The adaptation model of immunity: Is the goal of central tolerance to eliminate defective T cells or self-reactive T cells?Scandinavian journal of immunology · 2022Article
- NR4A family members regulate T cell tolerance to preserve immune homeostasis and suppress autoimmunity.JCI insight · 2021Article
- Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates.Nature communications · 2020Article
- Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis.Biomolecules · 2020Review
- T Cells and Regulated Cell Death: Kill or Be Killed.International review of cell and molecular biology · 2019Review
- Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.Immunology · 2018Article
- Dying to protect: cell death and the control of T-cell homeostasis.Immunological reviews · 2017Review
- Temporal Expression of Bim Limits the Development of Agonist-Selected Thymocytes and Skews Their TCRβ Repertoire.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Specialized proteasome subunits have an essential role in the thymic selection of CD8(+) T cells.Nature immunology · 2016Article
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
- mir-181a-1/b-1 Modulates Tolerance through Opposing Activities in Selection and Peripheral T Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Article
- T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity.eLife · 2014Article
- The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function.Nature immunology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Positive and negative selection of thymocytes in the thymus are critical for the development of a mature and self-tolerant T-cell repertoire. The proapoptotic Bcl-2 family member Bim is important for negative selection by inducing apoptosis in thymocytes receiving a strong signal through their antigen receptor. However, in the case of ubiquitous self-antigens (UbA), Bim is not required for the clonal deletion of self-reactive thymocytes, suggesting the existence of nonapoptotic clonal deletion mechanisms. Unlike UbA, clonal deletion to tissue-restricted antigens (TRAs) requires positive selection and CCR7-mediated migration to the medulla. This led us to hypothesize that Bim is required for the latter. To study the role of Bim in clonal deletion to TRA, we constructed bone marrow (BM) chimeras using OT-I Bim-deficient or -sufficient donor bone marrow and recipients that express membrane bound chicken ovalbumin under control of the rat insulin promoter (Rip-mOVA). We found that clonal deletion to TRA was completely abrogated in the absence of Bim and large numbers of mature OT-I CD8 T cells survived in the periphery. Despite the large numbers of autoreactive T cells, the chimeras did not develop diabetes and OT-I Bim-deficient T cells from these chimeras were functionally impaired. Collectively, these data provide unique evidence of a differential, thymocyte-intrinsic, molecular requirement downstream of the T-cell receptor (TCR) for clonal deletion to UbA versus TRA and highlight the profound ability of other tolerance mechanisms to control T-cell autoreactivity in the absence of thymic clonal deletion.
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