IKK beta is essential for protecting T cells from TNF alpha-induced apoptosis

Transcription factor NF-KB, whose activation depends on the IKK beta cataly tic subunit of the I kappaB kinase, was assigned with both anti- and proapo ptotic 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 thym ic rudiments, aberrant lymphoid organs, and absence of T cells. T lymphopoi esis is rescued when Ikk beta (-/-) stem cells are cotransferred with wt bo ne 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 sensitivi ty.