Research ArticleImmunology

Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell Proliferation

Sci. Signal.  26 Jun 2012:
Vol. 5, Issue 230, pp. ra46
DOI: 10.1126/scisignal.2002796

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PD-1 Inhibits the Cell Cycle Machinery

Effector T cells are stimulated through the T cell receptor (TCR) to become activated and proliferate. However, inhibitory receptors, such as PD-1, counteract these stimulatory signals and block T cell proliferation. Patsoukis et al. found that PD-1–mediated inhibition of Akt and Ras signaling pathways affected a number of components of the cell cycle machinery to “lock” T cells in the G1 phase and prevent their proliferation. These mechanistic details may help in the development of therapeutics designed to block PD-1 function and enable T cell activation in the context of antiviral or antitumor responses.