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.
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.
Zeng
Hu
H
Model Animal Research Center, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 225001, China.
Chen
Yuhong
Y
Yu
Mei
M
Xue
Liquan
L
Gao
Xiang
X
Morris
Stephan W
SW
Wang
Demin
D
Wen
Renren
R
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12