The death domain kinase RIP protects thymocytes from XXXX necrosis factor receptor type 2-induced cell death.

@entity5 @entity1131 @entity19 @entity1961 @entity20081 @entity70902
Fas and the @entity5 necrosis factor receptor ( @entity20081 regulate the programmed cell death of lymphocytes. The death domain kinase, receptor interacting protein (rip), is recruited to the @entity20081 upon receptor activation. In vitro, rip-/- fibroblasts are sensitive to TNF-induced cell death due to an impaired nuclear factor kappaB response. Because rip-/- @entity19 die at birth, we were unable to examine the effects of a targeted rip mutation on lymphocyte survival. To address the contribution of RIP to immune homeostasis, we examined lethally irradiated @entity19 reconstituted with rip-/- hematopoietic precursors. We observed a decrease in rip-/- thymocytes and T cells in both wild-type @entity70902 -/- irradiated hosts. In contrast, the B cell and myeloid lineages are unaffected by the absence of rip. Thus, the death domain kinase rip is required for T cell development. Unlike Fas-associated death domain, rip does not regulate T cell proliferation, as rip-/- T cells respond to polyclonal activators. However, @entity1131 @entity19 contain few viable @entity1961 + and CD8+ thymocytes, and rip-/- thymocytes are sensitive to TNF-induced cell death. Surprisingly, the rip-associated thymocyte apoptosis was not rescued by the absence of @entity20081 , but appears to be rescued by an absence of @entity20081 . Taken together, this study implicates RIP and @entity20081 in thymocyte survival.
