Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo.
T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma-dominant) or type 2 (IL-4-, IL-5-dominant) patterns. To investigate mechanisms that connect extracellular stimuli with the regulation of effector T cell function, we have measured immune responses of transgenic mice whose NF-kappa B/Rel signaling pathway is inhibited in T cells. Surprisingly, these mice developed type 2 T cell-dependent responses (IgE and eosinophil recruitment) in a model of allergic pulmonary inflammation. In contrast, type 1 T cell responses were severely impaired, as evidenced by markedly diminished delayed-type hypersensitivity responses, IFN-gamma production, and Ag-specific IgG2a levels. Taken together, these data indicate that inhibition of NF-kappa B can lead to preferential impairment of type 1 as compared with type 2 T cell-dependent responses.
Aronica
M A
MA
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232, USA.
Mora
A L
AL
Mitchell
D B
DB
Finn
P W
PW
Johnson
J E
JE
Sheller
J R
JR
Boothby
M R
MR
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D020672:I-kappa B Proteins; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D051996:Transcription Factor RelA
D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007132:Immunoglobulin Isotypes; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha