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Differential Dependence of CD4+ CD25+ Regulatory and Natural Killer-Like T Cells on Signals Leading to NF-κB Activation
Ist Teil von
Proceedings of the National Academy of Sciences - PNAS, 2004-03, Vol.101 (13), p.4566-4571
Ort / Verlag
National Academy of Sciences
Erscheinungsjahr
2004
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Natural killer-like (NK) T, regulatory T ( T R), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of T R cells and, to a lesser extent, of memory type T cells, depends on IκB kinase 2. Here, we show that T cell-specific ablation of IκB kinase 2, in addition, completely precludes NKT cell development. T cell antigen receptor (TCR)-induced signals to activate NF-κB are essential for mature T cell activation, leading us to hypothesize that this pathway could play an important role in the generation of the antigen-driven T cell subsets comprising T R, memory type T, and NKT cells. TCR-mediated NF-κB activation critically depends on Bcl10 and PKCθ. By using mice deficient for these proteins, we demonstrate that the generation of T R and, to a lesser extent, of memory type T cells, depends on Bcl10 and PKCθ, and therefore, most likely on NF-κB activation initiated by TCR engagement. NKT cells, on the other hand, require PKCθ for thymic development, whereas absence of Bcl10 leads primarily to the reduction of peripheral NKT cell numbers.