Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 13, Pages 4566-4571Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0400885101
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- NIAID NIH HHS [R01 AI057947, AI057947] Funding Source: Medline
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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 IkappaB kinase 2. Here, we show that T cell-specific ablation of IkappaB kinase 2, in addition, completely precludes NKT cell development. T cell antigen receptor (TCR)-induced signals to activate NF-kappaB 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-kappaB activation critically depends on Bcl10 and PKCtheta. 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 PKCtheta, and therefore, most likely on NF-kappaB activation initiated by TCR engagement. NKT cells, on the other hand, require PKCtheta for thymic development, whereas absence of Bcl10 leads primarily to the reduction of peripheral NKT cell numbers.
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