T cell receptor-mediated activation of CD4+CD44hi T cells bypasses Bcl10: an implication of differential NF-kappaB dependence of naïve and memory T cells during T cell receptor-mediated responses. J Biol Chem 2008 Sep 05;283(36):24392-9
Date
06/28/2008Pubmed ID
18583339Pubmed Central ID
PMC2528987DOI
10.1074/jbc.M802344200Scopus ID
2-s2.0-54049097968 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Previous studies have demonstrated that Bcl10 (B-cell leukemia/lymphoma 10) is essential for T cell receptor-mediated NF-kappaB activation and subsequent proliferation and interleukin 2 (IL2) production. However, here we demonstrate that, contrary to expectations, Bcl10 is differentially required for T cell activation, including for both proliferation and cytokine production. When CD4+ and CD8+ T cells were divided based on expression levels of CD44, which distinguishes naïve cells (CD44lo) versus those that are antigen-experienced (CD44hi), IL2 production by and proliferation of CD4+CD44lo naïve cells and both subpopulations of CD8+ T cells were clearly Bcl10-dependent, whereas these same functional properties of CD4+CD44hi T cells occurred largely independent of Bcl10. As with the other subpopulations of T cells, CD4+CD44hi T cells did not activate the NF-kappaB pathway in the absence of Bcl10; nevertheless, these CD4+CD44hi antigen-experienced T cells efficiently secreted IL2 after T cell receptor stimulation. Strikingly, therefore, T cell receptor-mediated IL2 production in these cells is NF-kappaB-independent. Our studies suggest that antigen-experienced CD4+ T cells differ from their naïve counterparts and from CD8+ T cells in their ability to achieve activation independent of the Bcl10/NF-kappaB pathway.
Author List
Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, Wen RAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
B-Cell CLL-Lymphoma 10 Protein
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Proliferation
Hyaluronan Receptors
Immunologic Memory
Interleukin-12
Lymphocyte Activation
Mice
Mice, Knockout
NF-kappa B
Receptors, Antigen, T-Cell
