Control Of Ifn-Gamma Production And Regulatory Function By The Inducible Nuclear Protein I Kappa B-Zeta In T Cells

The transcriptional regulator I kappa B-zeta is important for the control of apoptosis in keratinocytes. Thus, I kappa B-zeta-deficient mice develop autoimmune diseases, such as Sjogren's syndrome. However, T cells also play a pivotal role in Sjogren's syndrome. To study the role of I kappa B-zeta in T cells, we generated T cell-specific, I kappa B-zeta-deficient mice. We observed increased numbers of peripheral effector/memory CD4(+) cells and IFN-gamma-producing CD4(+) cells in 3-week-old mice. We found that I kappa B-zeta can be up-regulated by TGF-beta 1 in naive CD4(+) T cells and that it negatively regulates IFN-gamma expression. In addition, we generated T-reg-specific, I kappa B-zeta deficient mice and found that I kappa B-zeta is dispensable for the plasticity and stability of T-regs. However, T-regs from T cell-specific, I kappa B-zeta-deficient mice have reduced immunoregulatory function. Thus, our data reveal a previously unappreciated role for I kappa B-zeta in IFN-gamma production in T cells and the immunoregulatory function of T-regs.