Proposed model for the development of aberrant DNT cells in ALPS. Under normal conditions, CD4⁺ or CD8⁺ T cells can be eliminated by Fas/FasL interaction (black arrow). The majority of T cells in patients with ALPS-FAS show normal differentiation and normal mTOR activation, despite their defect in Fas signaling. Notably, a small fraction of CD4⁺ and CD8⁺ T cells show an abnormal differentiation and transcriptional program, enhanced mitotic activity, and hyperactive mTOR signaling (red arrow). Aberrant CD4⁺ and CD8⁺ T cells downregulate the coreceptor and convert to DNT cells, whereas the expression profile remains constant. Hyperactive mTOR pathway in Fas-deficient cells leads to expansion of pathognomonic DNT cells and chronic lymphoproliferation. Rapamycin therapy is able to control mTOR activity in both DNT cells and their precursors, resulting in reduced proliferation and increased apoptosis of aberrant cells.