Brain, Vol. 119, No. 2, 651-659, 1996
© 1996 Oxford University Press
research-article |
Antigen presentation by astrocytes primes rat T lymphocytes for apoptotic cell death
A model for T–cell apoptosis in vivo
1Department of Neurology, Clinical Research Unit for Multiple Sclerosis, Julius-Maximilians-Universität, Wurzburg 2Department of Neuroimmunology, Max Planck Institute for Psychiatry, Martinsried Germany 3Research Unit for Experimental Neuropathology, Austrian Academy of Sciences Vienna, Austria 4Division of Neurorehabilitation, Department of Neurology, University of Vienna Vienna, Austria
Correspondence to:
Correspondence to: Dr Ralf Gold, Neurologische Universitätsklinik, Josef-Schneider-Straße 11, D-97080 Würzburg, Germany
In this study we have characterized apoptotic cell death of autoreactive T cells resulting from their interaction with astrocytes and the modulatory effect of steroid hormones. Time kinetics of T-cell activation by interferon (IFN)-
-treated astrocytes from neonatal Lewis rats and by professional antigen presenting cells (APCs) from bulk suspensions of thymus or spleen were performed. [3H]Thymidine incorporation of neuritogenic P2- and encephalitogenie myelin basic protein (MBP)-specific T-cell lines declined after 48 h in culture with astrocytes. A similar suppressive effect was observed when T cells were cocultured with thymic APCs and astrocytes. This effect disappeared when astrocytes were separated by a transwell system. After 72 h of culture with astrocytes a mean of 17.5±12.4% T cells exhibited morphological signs of apoptosis. Apoptosis was identified by light microscopy, and confirmed by electron microscopy, by in situ tailing reaction and by agarose gel electrophoresis. Glucocorticosteroids and oestrogen specifically enhanced T-cell apoptosis within 8 h (69.8±23.1% and 69±17.1%, respectively) when added after 72 h to the astrocyte system, but not at earlier time points of T-cell activation or when thymic APCs were used. Glucocorticoid-mediated T-cell apoptosis was inhibited by the steroid-receptor antagonist RU 486. Pregnenolone, lipocortin-1, indomethacin and transforming growth factor-ß did not induce apoptosis in this system. The steroid effect was not associated with CD28, IL-2 receptor, or transferrin-receptor expression, which were equally upregulated on T cells activated by astrocytes or thymic APC as shown by fluorescence activated cell sorting (FACS) analysis. We conclude that astrocytes as CNS-specific APC may render T cells susceptible for induction of apoptotic cell death. Some steroid hormones can markedly enhance this process in vitro and may augment an additional effect of a systemic corticosteroid response in vivo during recovery from autoimmune encephalomyelitis.
apoptosis; encephalomyelitis; glucocorticoids; multiple sclerosis
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*These authors contributed equally
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