Transplantation of H-2kb-Transgenic Adrenocortical Cells in the Mouse Having Undergone an Adrenalectomy

Abstract

In conclusion, a model of cellular adrenocortical transplantation was established. The results show that syngeneic transplantation resulted in physiological corticosterone levels early after transplantation, whereas fully MHC-incompatible grafts were rejected. Recipients of Kb-transgenic grafts showed unimpaired adrenocortical function, but did not tolerize toward Kb-transgenic skin grafts. Possible mechanisms include a local immunomodulatory effect of glucocorticoids secreted by the graft and a low immunogenicity of the relatively small numbers of transplanted cells.

Allogeneic adrenocortical transplantation: glucocorticosteroid-independent immunomodulatory properties of adrenal cortex cells

“…Our research group previously demonstrated that selected allografts (adrenal cortex cells and pancreatic islet cells) with an isolated MHC class I disparity survive indefinitely (4,10). These results were confirmed by Kneteman et al who reported that MHC class I up-regulation is not associated with an acceleration of pancreatic islet cell rejection (11).…”

“…ANDREA SCHNEIDER, 1 MASOUMEH ATTARAN, 1 KLAUS F. GRATZ, 2 JOERG S. BLECK, 1 MICHAEL WINKLER, 3 MICHAEL P. MANNS, 1 AND MICHAEL OTT 1,4 Background. Partial correction of metabolic liver disease by hepatocyte transplantation requires infusion of a large number of cells into the portal vein.…”

“…Applications have been reported in patients with acute liver failure, in chronic liver disease, and recently in a patient with hereditary hyperbilirubinemia (1)(2)(3)(4)(5)(6)(7). Hepatocytes can be transplanted into the liver through the portal vein, into the spleen, or into the peritoneal cavity (8 -10).…”

“…One hundred days after adrenocortical transplantation, both graft recipients and sham-operated control animals equally revealed physiologic basal corticosterone levels and, noticeably, demonstrated increased serum corticosterone levels after adrenocorticotropic hormone stimulation (5). Conversely, acute graft rejection and early postoperative death (within 8 days) was observed after transplantation of K b transgenic adrenal cells into anti-K b T-cell receptor (Des-TCR) transgenic recipients (4). To evaluate the underlying mechanisms of the detected graft protection of MHC class I disparate adrenocortical grafts, we established an in vitro culture model and examined the immunomodulatory role of local cortisol secretion of adrenal cortex cells.…”

“…In previous studies, our research group investigated the immunologic responses in a defined mouse model using major histocompatibility complex (MHC) class I (H-2K b , K b ) transgenic mice with an isolated MHC class I disparity between donor and recipient (4). Adrenalectomized recipients of MHC class I disparate adrenocortical grafts survived indefinitely without any immunosuppression and demonstrated physiologic corticosterone levels on days 20, 50, and 100 posttransplantation.…”