Preferential Role for NF-κB/Rel Signaling in the Type 1 But Not Type 2 T Cell-Dependent Immune Response In Vivo

Abstract 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-γ-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-κB/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-γ production, and Ag-specific IgG2a levels. Taken together, these data indicate that inhibition of NF-κB can lead to preferential impairment of type 1 as compared with type 2 T cell-dependent responses.