Article ; Online: Protein phosphatase 2A B55β limits CD8+ T cell lifespan following cytokine withdrawal.
The Journal of clinical investigation
2020 Volume 130, Issue 11, Page(s) 5989–6004
Abstract: How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55β, a regulatory subunit of protein phosphatase 2A, represents a molecular ... ...
| Abstract | How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55β, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55β induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55β and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory. |
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| MeSH term(s) | Animals ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/immunology ; CD8-Positive T-Lymphocytes/immunology ; Immunologic Memory ; Mice ; Mice, Transgenic ; Neuropeptides/genetics ; Neuropeptides/immunology ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/immunology ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/immunology | |||||
| Chemical Substances | Apoptosis Regulatory Proteins ; Hrk protein, mouse ; Neuropeptides ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Protein Phosphatase 2 (EC 3.1.3.16) | |||||
| Language | English | |||||
| Publishing date | 2020-08-04 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 3067-3 | |||||
| ISSN | 1558-8238 ; 0021-9738 | |||||
| ISSN (online) | 1558-8238 | |||||
| ISSN | 0021-9738 | |||||
| DOI | 10.1172/JCI129479 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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