The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens
- Authors: Gray, Daniel , Kupresanin, Fiona , Berzins, Stuart , Herold, Marco , O'Reilly, Lorraine , Bouillet, Philippe , Strasser, Andreas
- Date: 2012
- Type: Text , Journal article
- Relation: Immunity Vol. 37, no. 3 (September 2012), p. 451-462
- Full Text: false
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- Description: Although the proapoptotic BH3-only protein, Bim, is required for deletion of autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ-specific autoimmune disease. To determine whether other BH3-only proteins safeguard tolerance in the absence of Bim, we screened mice lacking Bim as well as other BH3-only proteins. Most strains showed no additional defects; however, mice deficient for both Puma and Bim spontaneously developed autoimmunity in multiple organs, and their T cells could transfer organ-specific autoimmunity. Puma- and Bim-double-deficient mice had a striking accumulation of mature, single-positive thymocytes, suggesting an additional defect in thymic deletion was the basis for disease. Transgenic mouse models of thymocyte deletion by peripheral neoantigens confirmed that the loss of Bim and Puma allowed increased numbers of autoreactive thymocytes to escape deletion. Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease.
- Description: C1
The NF-κB1 transcription factor prevents the intrathymic development of CD8 T cells with memory properties
- Authors: Gugasyan, Raffi , Horat, Elisha , Kinkel, Sarah , Ross, Fiona , Grigoriadis, George , Gray, Daniel , O'Keeffe, Meredith , Berzins, Stuart , Belz, Gabrielle , Grumont, Raelene , Banerjee, Ashish , Strasser, Andreas , Godfrey, Dale , Tsichlis, Phillip , Gerondakis, Steve
- Date: 2012
- Type: Text , Journal article
- Relation: EMBO Journal Vol. 31, no. 3 (2012), p. 692-706
- Full Text: false
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- Description: The role of specific members of the NF-κB family of transcription factors in CD8 T-cell selection and development is largely unknown. Here, we show that mice lacking NF-κB1 develop a unique population of conventional CD8 single-positive (SP) thymocytes with memory T cell-like properties that populate peripheral immune organs. Development of this memory-like population is not due to PLZF + thymocytes and instead coincides with changes in CD8 T-cell selection. These include a reduction in the efficiency of negative selection and a dependence on MHC class Ia or Ib expressed by haematopoietic cells. These findings indicate that NF-κB1 regulates multiple events in the thymus that collectively inhibit the excess development of CD8 + thymocytes with memory cell characteristics. © 2012 European Molecular Biology Organization | All Rights Reserved.
Distinct subpopulations of DN1 thymocytes exhibit preferential gamma delta T lineage potential
- Authors: Oh, Seungyoul , Liu, Xin , Tomei, Sara , Luo, Mengxiao , Skinner, Jarrod , Berzins, Stuart , Naik, Shalin , Gray, Daniel , Chong, Mark
- Date: 2023
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 14, no. (2023), p.
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- Description: The