Open AccessDifferential dependence of CD4 + CD25 + regulatory and natural killer-like T cells on signals leading to NF-κB activation
Author(s) -
Marc Schmidt-Supprian,
Jane Tian,
Ethan P. Grant,
Manolis Pasparakis,
René Maehr,
Huib Ovaa,
Hidde L. Ploegh,
Anthony J. Coyle,
Klaus Rajewsky
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0400885101
Subject(s) - natural killer t cell , il 2 receptor , t cell , biology , microbiology and biotechnology , t cell receptor , zap70 , cd28 , cytotoxic t cell , jurkat cells , bcl10 , immunology , immune system , in vitro , biochemistry , lymphoma
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 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 TR, 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 TR 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.