| First Author | Schuh K | Year | 1998 |
| Journal | Eur J Immunol | Volume | 28 |
| Issue | 8 | Pages | 2456-66 |
| PubMed ID | 9710223 | Mgi Jnum | J:110686 |
| Mgi Id | MGI:3640882 | Doi | 10.1002/(SICI)1521-4141(199808)28:08<2456::AID-IMMU2456>3.0.CO;2-9 |
| Citation | Schuh K, et al. (1998) Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice. Eur J Immunol 28(8):2456-66 |
| abstractText | 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. |
