Ellerkamp V, Musholt T J, Klebs S H, Musholt P B, Scheumann G F, Klempnauer J, Hoffmann M W
Department of Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
Surgery. 2000 Dec;128(6):999-1006. doi: 10.1067/msy.2000.110241.
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.
Major histocompatibility complex (MHC) class I transgenic mice were used for the implementation of an animal model of adrenocortical cell transplantation in adrenalectomized mice. K(b)-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).
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 K(b)-disparate spleen cells was also abolished in the presence of adrenocortical cells. This effect, however, could not be reversed by mifepristone.
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.
激素替代疗法用于治疗肾上腺皮质功能不全（艾迪生病）时，无法充分替代应激状态下所需的激素峰值。因此，肾上腺皮质同种异体移植可能是一种有趣的替代方法。
利用主要组织相容性复合体（MHC）I类转基因小鼠建立肾上腺切除小鼠肾上腺皮质细胞移植的动物模型。将K(b)转基因细胞和同种异体肾上腺皮质细胞在混合淋巴细胞培养物中共培养，以检测同种异体免疫反应。来自T细胞受体转基因小鼠和正常同种异体小鼠的淋巴细胞作为反应细胞。肾上腺皮质细胞分泌的皮质类固醇的作用被类固醇受体拮抗剂米非司酮（RU486）拮抗。
体外共培养实验表明，MHC I类不同的肾上腺皮质细胞未能激活B10.BR和T细胞受体转基因淋巴结细胞。在米非司酮存在的情况下，这种抑制作用被拮抗，导致淋巴细胞强烈增殖。在肾上腺皮质细胞存在的情况下，K(b)不同的脾细胞对B10.BR淋巴细胞的激活也被消除。然而，这种作用不能被米非司酮逆转。
在体外，肾上腺皮质细胞的存在有力地抑制了同种异体免疫反应。这种作用仅部分归因于皮质类固醇的分泌，表明肾上腺皮质细胞具有额外的免疫调节特性。
