Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-κB activation

M Schmidt-Supprian, J Tian, EP Grant… - Proceedings of the …, 2004 - National Acad Sciences
M Schmidt-Supprian, J Tian, EP Grant, M Pasparakis, R Maehr, H Ovaa, HL Ploegh
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface
phenotypes reminiscent of activated T cells. Previously, we reported that the generation of
TR 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 …
Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of TR 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 TR, 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 TR 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.
National Acad Sciences