Allogeneic adrenocortical transplantation: glucocorticosteroid-independent immunomodulatory properties of adrenal cortex cells.
BACKGROUND
Hormone substitution for the treatment of adrenocortical insufficiency does not adequately substitute the physiologic circadian secretion of corticosteroids and leads to long-term sequelae and reduced quality of life. The lack of adaptation to physical and psychologic stress situations may lead to life-threatening Addison's crises. Allogeneic transplantation of adrenal cortex could offer an intriguing alternative. Adrenocortical grafts were demonstrated to proliferate and produce corticosteroids in physiologic concentrations after transplantation.


METHODS
K -transgenic murine lymphocytes and allogeneic adrenal cortex cells were cocultured in mixed lymphocyte reactions to examine the alloimmune response; lymphocytes from T-cell receptor transgenic mice and normal mice, respectively, served as responder cells. The effects of corticosteroids secreted by adrenocortical cells were antagonized by the steroid receptor antagonist mifepristone, whereas the impact of cell-cell interactions was differentiated with transwell culture systems.


RESULTS
Coculture of adrenal cortex cells in mixed lymphocyte reactions markedly suppressed lymphocyte proliferation. Transwell cultures demonstrated that adrenocortical cells exerted their effects by a soluble factor that was only partially antagonized by mifepristone.


CONCLUSIONS
In vitro, the presence of adrenocortical cells potently suppressed allogeneic immune responses. This effect was not exclusively the result of the secretion of corticosteroids, indicating an additional immunomodulatory property of adrenocortical cells.
Musholt
Thomas J
TJ
Department of Visceral and Transplantation Surgery, Hannover University Medical School, 30625 Hannover, Germany.
Ellerkamp
Verena
V
Musholt
Petra B
PB
Klebs
Sven H G
SH
Klempnauer
Juergen
J
Hoffmann
Matthias W
MW
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000302:Adrenal Cortex / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005938:Glucocorticoids / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D011948:Receptors, Antigen, T-Cell