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Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo.

Aronica MA, Mora AL, Mitchell DB, Finn PW, Johnson JE, Sheller JR, Boothby MR
J Immunol. 1999 163 (9): 5116-24

PMID: 10528218

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.

MeSH Terms (22)

Animals Bronchial Hyperreactivity Cell Movement Cytokines DNA-Binding Proteins Eosinophilia Hypersensitivity, Delayed I-kappa B Proteins Immunoglobulin Isotypes Lung Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Proto-Oncogene Proteins c-rel Respiratory Hypersensitivity Th1 Cells Th2 Cells Transcription Factor RelA

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