Proposed mechanism for immunodeficiency because of MST1 defects. MST1-deficient humans and mice exhibit significantly restricted populations of naive T cells. This is likely due to impairment of at least 2 primary roles of MST1: (1) mediation of TCR (black receptor) and chemokine (green circle) driven integrin (LFA1) activation (purple crescent), necessary for T-cell adhesion and (2) activation of Foxo1, necessary for IL-7Rα transcription. In MST1 deficiency, unopposed AKT activity leads to phosphorylation and cytoplasmic shuttling of Foxo1 and impaired transcription of IL-7Rα, decreasing the sensitivity of naive T cells to IL-7. Naive T-cell survival is dependent on TCR and IL-7 exposure in the lymph node. In MST1 deficiency, lymph node entry is impaired because of poorly activated LFA1 (blue semicircles); IL-7R (blue squares) signaling is diminished; and T-cell stimulation by antigen-presenting cells (APCs) is suboptimal (also due to impaired LFA1 activation). Therefore, naive T cells die and effector cells undergo suboptimal activation and proliferation.