IKKbeta is Essential for Protecting T Cells from TNFalpha-induced Apoptosis

Transcription factor NF-kappaB, whose activation depends on the IKKbeta catalytic subunit of the IkappaB kinase, was assigned with both anti- and proapoptotic functions in T lymphocytes. To critically evaluate these functions, we transferred Ikkbeta-/- or wild-type (wt) fetal liver (FL) stem cells into lethally irradiated mice. Ikkbeta-/- radiation chimeras show thymic rudiments, aberrant lymphoid organs, and absence of T cells. T lymphopoiesis is rescued when Ikkbeta-/- stem cells are cotransferred with wt bone marrow, suggesting that IKKbeta may mediate its lymphopoietic function via extrinsic factors. However, almost normal development of Ikkbeta-/- T cells is observed upon removal of type 1 TNFalpha receptor, indicating that TNFalpha signaling accounts for the absence of Ikkbeta-/- T cells. Indeed, Ikkbeta-/- radiation chimeras exibit elevated circulating TNFalpha, and Ikkbeta-/- thymocytes display increased TNFalpha sensitivity.