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

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 1

B55β regulates survival of activated T cells.

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B55β regulates survival of activated T cells.
A quantity of 106 OT-I CD4...
A quantity of 106 OT-I CD45.2+ Ppp2r2b+/+ Cd4.Cre+ (WT) or Ppp2r2bfl/fl Cd4.Cre+ (cKO) cells were adoptively transferred into WT CD45.1+ mice. The next day, 104 CFU of ovalbumin-expressing Listeria monocytogenes (LM-OVA) were i.v. injected into the recipient mice. (A) OT-I cells (CD45.2+ CD8+ Vα2+ Vβ5+) quantified in the spleens of recipient mice before infection (Basal) and at the indicated time points. (B) Frequency of naive (CD44– CD62L+), EM (CD44+ CD62L–), and CM (CD44+ CD62L+) cells within donor-derived OT-I cells. (C) OT-I EM and CM cell numbers in spleens of recipient mice are quantified at the indicated time points. Each symbol represents a mouse. Mean and SEM are indicated by horizontal lines. (D) Representative dot plots of CD127 (IL-7Rα) and KLGR1 expression on adoptively transferred OT-I cells at day 7 after infection with LM-OVA. Numbers in the dot plots represent the mean ± SEM of the indicated populations. (E) Absolute numbers of OT-I CD127+ KLGR1– and CD127– KLGR1+ cells in spleens of recipient mice. (F) Spleen cells from infected mice, stimulated ex vivo with SIINFEKL, in the presence of Brefeldin A. Results are expressed as absolute numbers of IFN-γ–producing OT-I T cells (mean ± SEM). (G) Representative contour plots from spleen cells stimulated with SIINFEKL (gated in CD45.2+ CD8+ Vα2+ Vβ5+ donor-derived OT-I cells). Numbers represent mean ± SEM of the IFN-γ+ populations. Results from 1 representative of 3 experiments (n = 3–5 mice/group) are shown (A–G). For comparison of the means, unpaired 2-tailed t tests were used in A, C, E, and F; **P ≤ 0.01, ***P ≤ 0.001.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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