Details

Autor(en) / Beteiligte

• Schmidt-Supprian, Marc
• Tian, Jane
• Grant, Ethan P.
• Pasparakis, Manolis
• Maehr, René
• Ovaa, Huib
• Ploegh, Hidde L.
• Coyle, Anthony J.
• Rajewsky, Klaus

Titel

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.