International Immunology, Vol. 12, No. 6, 817-824,
June 2000
© 2000 Japanese Society for Immunology
Impaired Ca/calcineurin pathway in in vivo anergized CD4 T cells
Department of Molecular Immunology, Graduate School of Medicine, Chiba University and
1 Department of Developmental Immunology, Chiba University School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan
2 Research Institute for Biological Sciences and
3 Department of Bioengineering, Science University of Tokyo, 2669 Yamazaki, Chiba 279-0022, Japan.
4 Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2600, USA
5 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Correspondence to: T. Nakayama
Clonal anergy is one of the mechanisms that may account for self tolerance induced in T cells in the periphery. In this study we used the well-documented system of in vivo administration of a superantigen, staphylococcal enterotoxin B (SEB), to induce a state of hyporesponsiveness (anergy) in murine peripheral T cells to decipher the intracellular biochemical basis for this process. The TCR-induced Ca response of in vitro activated T cells was found to be impaired with significant defects in the phosphorylation of phospholipase C-
1. Experiments with calcium ionophore and newly established transgenic mouse lines that express an active form of calcineurin suggested that in vivo SEB-induced anergy is established and/or maintained by a selective impairment in the TCR-induced activation of the Ca/calcineurin pathway.
Keywords: active calcineurin transgenic, anergy, calcineurin, calcium, peripheral tolerance, superantigen
Transmitting editor: A. Singer
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