Essential role of IκB(NS) for in vivo CD4(+) T‐cell activation, proliferation, and Th1‐cell differentiation during Listeria monocytogenes infection in mice

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, IκB(NS,) is involved in the development of Th1, Th17, and regulatory T (Treg) cells. However, it remained unclear to which extend IκB(NS) contributed 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 antigen‐specific activation of CD4(+) T cells following in vivo pathogen encounter to strongly rely on IκB(NS). While IκB(NS) was largely dispensable for the acquisition of cytotoxic effector function in CD8(+) T cells, IκB(NS)‐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 IFN‐γ, IL‐2, and TNF‐α. Complementary in vitro analyses using cells from novel reporter and inducible knockout mice revealed that IκB(NS) predominantly affects the early phase of Th1‐cell differentiation while its function in terminally differentiated cells appears to be negligible. Our data suggest IκB(NS) as a potential target to modulate specifically CD4(+) T‐cell responses.