1998/08/01 by Kai Schuh, Burkhard Kneitz, Jörg Heyer +9 · 5 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Antibody #Apoptosis #B cell #Biochemistry #Biology #Cell biology #Germinal center #Immune Cell Function and Interaction #Immune system #Immunology #Involution (esoterism) #NF-κB Signaling Pathways #Signaling Pathways in Disease #T cell #Thymic involution
paper · doi:10.1002/(sici)1521-4141(199808)28:08<2456::aid-immu2456>3.0.co;2-9
openalex publication_date 1998/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25
NF-ATp and NF-ATc are the most prominent nuclear NF-AT transcription factors in peripheral T lymphocytes. After T cell activation both factors bind to and control the promoters and enhancers of numerous lymphokine and receptor ligand genes. In order to define a specific role for NF-ATp in vivo we have inactivated the NF-ATp gene by gene targeting in mice. We show that NF-ATp deficiency leads to the accumulation of peripheral T cells with a "preactivated" phenotype, enhanced immune responses of T cells after secondary stimulation in vitro and severe defects in the proper termination of antigen responses, as shown by a reduced deletion of superantigen-reactive CD4+ T cells. These alterations in the function of the immune system are correlated with drastic changes in the morphology of lymphoid organs. Approximately 25 % of NF-ATp-deficient mice older than 6 months develop large germinal centers in the spleen and peripheral lymph nodes. In addition, they exhibit a pronounced retardation in the involution of the thymus. The thymus of these NF-ATp-deficient mice exhibits large cortical areas typical for newborn mice and a massive infiltration of IgM+/ IgD+ B lymphocytes. Contrary to the T lymphocytes from IL-2-deficient mice which develop a phenotype similar to the NF-ATp-/- mice, NF-ATp-/- T cells do not show obvious defects in Fas-mediated apoptosis. This might indicate defects in other types of programmed cell death which are controlled by the activity of NF-ATp.