Tissue Culture Reduces la Antigen-bearing Cells in Rat Islets and Prolongs Islet Allograft Survival

Abstract

Prolongation of rat pancreatic islet allograft survival by a prior 7-day period of tissue culture was demonstrated, confirming previous reports by others. We then sought to identity those cells in islets capable of stimulating allograft rejection (Ia antigen-bearing cells) and to determine whether such cells and/or their Ia antigens might be reduced by tissue culture. Freshly isolated and 7-day-cultured Wistar-Furth rat islets were incubated with a mouse anti-rat Ia nonpolymorphic monoclonal antibody, then with peroxidase-conjugated goat anti-mouse antibody, and processed for electron microscopy. Peroxidase (Ia)-positive lymphocytes, macrophages, and capillary endothelial cells were identified in fresh but not in cultured islets. A radioligand assay, using 125I-protein A, revealed a 45% decrease in binding of Ia antibody to cultured compared with fresh islet cells. We conclude that Ia antigen-bearing lymphocytes, macrophages, and capillary endothelial cells in rat islets are reduced by tissue culture and that this may account, at least in part, for the decreased immunogenicity of cultured islet allografts.

Resident Macrophages Mediate Islet Amyloid Polypeptide–Induced Islet IL-1β Production and β-Cell Dysfunction

“…staining (40,41). The present data suggest no change in the size of the islet macrophage population based on CD11b and F4/80 expression after 5 days in RPMI at 37°C, despite decreased MHC class II expression.…”

In Situ Ultrastructural Demonstration of Cells Bearing la Antigens in the Murine Pancreas

“…10 and this report). The situation in the rat is less clear, in that some investigators have reported la + endothelium, 8 while others have attributed la antigen expression in rat islets to cells of hematogenous origin. 11 12 It remains to be determined if transplantation of islets stimulates the expression of la antigens by endothelial cells within the graft as has been described for murine skin allog rafts.…”

“…In isolated rat islets, class II major histocompatibility antigens have been demonstrated at the ultrastructural level to be associated with lymphocytes, macrophages, and capillary endothelial cells. 8 In another report, capillary endothelial cells were considered to be the major source of HLA-DR antigens in human islets. 9 Ultrastructural immunocytochemistry of dissociated murine thyroid and islet cells indicated that neither glandular epithelium nor capillary endothelium expressed la antigens, but that a minor population of cells in both of these organ preparations reacted strongly with anti-la antibodies.…”

ASKP1240, a Fully Human Anti-CD40 Monoclonal Antibody, Prolongs Pancreatic Islet Allograft Survival in Nonhuman Primates

“…The discrepancy regarding the efficacy of ASKP1240 in the current PITx and in Tx models in other organs is likely caused by different immunological characteristics of the transplants. Pancreatic islets mainly consist of b cells that only express MHC class I, although low expression of MHC class II may exist because of contaminating leukocytes (28)(29)(30). …”