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Protein phosphatase 2A B55β limits CD8+ T cell lifespan following cytokine withdrawal
Noé Rodríguez-Rodríguez, … , Florencia Rosetti, José C. Crispín
Noé Rodríguez-Rodríguez, … , Florencia Rosetti, José C. Crispín
Published August 4, 2020
Citation Information: J Clin Invest. 2020;130(11):5989-6004. https://doi.org/10.1172/JCI129479.
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Research Article Autoimmunity Article has an altmetric score of 13

Protein phosphatase 2A B55β limits CD8+ T cell lifespan following cytokine withdrawal

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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.

Authors

Noé Rodríguez-Rodríguez, Iris K. Madera-Salcedo, J. Alejandro Cisneros-Segura, H. Benjamín García-González, Sokratis A. Apostolidis, Abril Saint-Martin, Marcela Esquivel-Velázquez, Tran Nguyen, Dámaris P. Romero-Rodríguez, George C. Tsokos, Jorge Alcocer-Varela, Florencia Rosetti, José C. Crispín

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Figure 5

B55β activates FoxO1 and promotes HRK transcription.

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B55β activates FoxO1 and promotes HRK transcription.
(A) MCF-7 cells wer...
(A) MCF-7 cells were transfected with a plasmid encoding a GFP-FoxO1 fusion protein and either pLVX-PPP2R2B-IRES-mCherry or pLVX-mCherry, and FoxO1 localization was evaluated by fluorescence microscopy. Representative images are shown. Arrows indicate cells transfected with both plasmids; arrowheads indicate cells transfected only with GFP-FoxO1. Scale bars: 5 μm. (B) Cumulative data (mean ± SEM) of 3 independent experiments are shown (each dot represents 1 experiment). In each experiment, 100 cotransfected cells were evaluated. For comparison of the means, unpaired 2-tailed t test was used; **P ≤ 0.01. (C) Human T cells were infected with control- or B55β-encoding lentiviruses following the procedure depicted in Figure 4. Sixteen hours later, expression of the indicated genes was quantified by real-time PCR and normalized to ACTB. Cumulative data of 8 independent experiments expressed as mean ± SEM fold induction against empty virus (indicated by the broken line). Each dot represents 1 sample. For comparison of the means, unpaired 2-tailed t test was used; *P ≤ 0.05, **P ≤ 0.01.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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