I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell help, germinal center reactions, and homeostatic expansion.
Signal transduction from proinflammatory stimuli leading to NF-kappa B-dependent gene expression is mediated by the I kappa B kinase 2 (IKK2/IKK beta). Therefore, IKK2 has become an important drug target for treatment of inflammatory conditions. T cells, whose activation depends to a large extent on the activity of NF-kappa B transcription factors, play important roles in inflammation and autoimmunity. Ablation of IKK2 specifically in T cells in CD4cre/Ikk2(FL) mice allows their survival and activation by polyclonal stimuli in vitro, suggesting that IKK2 is dispensable for T cell activation. We report in this study that IKK2-deficient T cells expand efficiently in response to superantigen administration in vivo, but are completely deficient in recall responses, most likely due to inefficient priming. IKK2-deficient T cells provide suboptimal B cell help and fail to support germinal center reactions. Finally, IKK2 is essential for homeostatic expansion of naive T cells, reflected by the inability of IKK2-deficient T cells to induce colitis in lymphopenic hosts.
Schmidt-Supprian
Marc
M
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA. supprian@cbr.med.harvard.edu
Tian
Jane
J
Ji
Hongbin
H
Terhorst
Cox
C
Bhan
Atul K
AK
Grant
Ethan P
EP
Pasparakis
Manolis
M
Casola
Stefano
S
Coyle
Anthony J
AJ
Rajewsky
Klaus
K
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology / Q000633:toxicity; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006706:Homeostasis; D051550:I-kappa B Kinase; D007114:Immunization; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse