Immune destruction of hematopoiesis. Antigens are presented to T lymphocytes by antigenpresenting cells (APCs), which trigger T cells to activate and proliferate. T-bet, a transcription factor, binds to the interferon-γ (INF-γ) promoter region and induces gene expression. SAP binds to Fyn and modulates SLAM activity on IFN-γ expression, diminishing gene transcription. Patients with aplastic anemia show constitutive T-bet expression and low SAP levels. IFN-γ and TNF-α up-regulate other T cells' cellular receptors and also the Fas receptor. Increased production of interleukin-2 leads to polyclonal expansion of T cells. Activation of Fas receptor by the Fas ligand leads to apoptosis of target cells. Some effects of IFN-γ are mediated through interferon regulatory factor 1 (IRF-1), which inhibits the transcription of cellular genes and entry into the cell cycle. IFN-γ is a potent inducer of many cellular genes, including inducible nitric oxide synthase (NOS), and production of the toxic gas nitric oxide (NO) may further diffuse toxic effects. These events ultimately lead to reduced cell cycling and cell death by apoptosis.