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Retarded thymic involution and massive germinal center formation in NF‐ATp‐deficient mice

Retarded thymic involution and massive germinal center formation in NF‐ATp‐deficient mice 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

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References (43)

Publisher
Wiley
Copyright
© 1998 WILEY‐VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany
ISSN
0014-2980
eISSN
1521-4141
DOI
10.1002/(SICI)1521-4141(199808)28:08<2456::AID-IMMU2456>3.0.CO;2-9
pmid
9710223
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

European Journal of ImmunologyWiley

Published: Aug 1, 1998

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