Acquisition of effector functions in T cells is guided by transcription factors including NF-κB that itself is tightly controlled by inhibitory proteins. The atypical NF-κB inhibitor IκBNS is involved in the development of Th1, Th17 and Treg cells. However, it remained unclear to which extend IκBNS contributes to the acquisition of effector function in T cells specifically responding to a pathogen during in vivo infection. Tracking of adoptively transferred T cells in Listeria monocytogenes infected mice uncovered antigen-specific activation of CD4+ T cells following in vivo pathogen encounter to strongly rely on IκBNS . While IκBNS was largely dispensable for the acquisition of cytotoxic effector function in CD8+ T cells, IκBNS -deficient Th1 effector cells exhibited significantly reduced proliferation, marked changes in the pattern of activation marker expression and reduced production of the Th1-cell cytokines IFNγ, IL2 and TNFα. Complementary in vitro analyses using cells from novel reporter and inducible knockout mice revealed that IκBNS predominantly affects the early phase of Th1-cell differentiation while its function in terminally differentiated cells appears to be negligible. Our data suggest IκBNS as a potential target to modulate specifically CD4+ T-cell responses. This article is protected by copyright. All rights reserved
