Essential role of IκB 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 is involved in the development of Th1, Th17, and regulatory T (Treg) cells. However, it remained unclear to which extend IκB 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 . While IκB was largely dispensable for the acquisition of cytotoxic effector function in CD8 T cells, IκB -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 predominantly affects the early phase of Th1-cell differentiation while its function in terminally differentiated cells appears to be negligible. Our data suggest IκB as a potential target to modulate specifically CD4 T-cell responses.