Abstract
Background. Hormone substitution for the treatment of adrenocortical insufficiency (Addison's
disease) does not adequately substitute the hormone peaks required in stress situations.
Therefore, allogeneic transplantation of adrenal cortex could offer an intriguing
alternative. Methods. Major histocompatibility complex (MHC) class I transgenic mice were used for the
implementation of an animal model of adrenocortical cell transplantation in adrenalectomized
mice. Kb-transgenic cells and allogeneic adrenocortical cells were cocultured in mixed lymphocyte
cultures to examine the alloimmune response. Lymphocytes from T-cell receptor transgenic
mice and normal allogeneic mice served as responder cells. The effect of corticosteroids
secreted by adrenocortical cells was antagonized by the steroid receptor antagonist
mifepristone (RU486). Results. In vitro coculture experiments showed that MHC class I disparate adrenocortical cells
failed to activate B10.BR and T-cell receptor transgenic lymph node cells. In the
presence of mifepristone this inhibitory effect was antagonized, resulting in strong
lymphocyte proliferation. Activation of B10.BR lymphocytes by Kb-disparate spleen cells was also abolished in the presence of adrenocortical cells.
This effect, however, could not be reversed by mifepristone. Conclusions. In vitro, the presence of adrenocortical cells potently suppressed allogeneic immune
responses. This effect was only in part due to the secretion of corticosteroids, pointing
to an additional immunomodulatory property of adrenocortical cells. (Surgery 2000;128:999-1006.)
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Article info
Footnotes
*Supported by grants of the Deutsche Forschungsgemeinschaft (M. W. H., T. J. M. and G. S.) (SFB 265-B10, Scheu358/3-2).
**Reprint requests: Matthias W. Hoffmann, MD, PhD, Klinik für Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, D-30623 Hannover, Germany.
★Surgery 2000;128:999-1006.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
