Evaluation of effect of PTEN gene deletion in mouse CD4+ Th1 clones after stimulation

PTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation. T cells from mice in which PTEN was conditionally deleted in the thymus were reported to display CD28-independent IL-2 production and relative resistance to anergy induction. However, such observations could have stemmed from alterations in T cell development due to early deletion in thymocytes. To directly eliminate PTEN in post-thymic T cells, we utilized CAR Tg x PTENflox/flox mice which enabled gene deletion using a Cre adenovirus in vitro. Gene expression profiling revealed a small subset of induced genes that were augmented upon PTEN deletion and T cell stimulation. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells. Nonetheless, PTEN inhibition may be a viable target for immune potentiation due to increased cytokine production by activated CD4+ cells.

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Locke FL, Zha YY, Zheng Y, Driessens G, Gajewski TF