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The costimulation-regulated duration of PKB activation controls T cell longevity

A Corrigendum to this article was published on 01 November 2004

Abstract

A brief antigenic stimulus can promote T cell proliferation, but the duration and nature of intracellular signals required for survival are unclear. Here we show that in the absence of OX40 costimulation, antigen-activated CD4+ cells are short-lived because the activity of protein kinase B (PKB; also known as Akt) is not maintained over time. Activated T cells that express a dominant-negative variant of PKB also undergo apoptosis, reproducing the OX40-deficient phenotype. In contrast, an active form of PKB prevents downregulation of antiapoptotic proteins in OX40-deficient T cells, rescues antigen-induced cell survival in vivo, and controls inflammation in recall responses. Thus, sustained and periodic PKB signaling has an integral role in regulating T cell longevity.

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Figure 1: OX40 signals maintain PKB phosphorylation over time and are required for long-term survival of antigen-stimulated CD4+ cells.
Figure 2: OX40 signals sustain PKB kinase activity.
Figure 3: Retroviral transduction of OX40-deficient T cells with active PKB reverses their survival defect.
Figure 4: PKB regulates the expression of Bcl-xL, Bcl-2 and Bfl-1 and suppresses apoptosis.
Figure 5: PKB restores the survival of OX40-deficient T cells in secondary responses in vitro.
Figure 6: Sustained PKB controls T cell survival in vivo.
Figure 7: Sustained PKB does not alter T cell reactivity in vivo.
Figure 8: Sustained PKB restores the ability of OX40-deficient T cells to promote lung inflammation.

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Acknowledgements

This work was supported by grants from the NIH (CA91827 and AI50498) and the Sandler Program for Asthma Research (to Mi.C.). This is manuscript number 534 from the La Jolla Institute for Allergy and Immunology.

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Correspondence to Michael Croft.

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Song, J., Salek-Ardakani, S., Rogers, P. et al. The costimulation-regulated duration of PKB activation controls T cell longevity. Nat Immunol 5, 150–158 (2004). https://doi.org/10.1038/ni1030

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