IKKβ is essential for protecting T cells from TNFα-induced apoptosis

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