Illustration of how killing of thymic epithelial cells (TECs) by alloreactive T lymphocytes can lead to posttransplantation immune deficiency. Alloreactive primed or unprimed naive T lymphocytes enter the recipient thymus after HSCT. As a result of T-cell receptor–mediated recognition of alloantigens presented by the TECs, the alloreactive T cells secrete interferon-gamma (IFN-γ). The TEC response to interferon signaling includes activation of the STAT1 transcription factor, leading to an apoptotic program and TEC death. The loss of TECs results in defective microenvironmental support of thymopoiesis via numerous molecules such as the Notch ligand Dll1, the cytokines IL-7 and Kit ligand (KL), and the chemokines TECK and CXCL12. The resultant decrease in T-cell production ultimately leads to immune deficiency.