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Diabetes, Vol 40, Issue 7 809-814, Copyright © 1991 by American Diabetes Association

ARTICLES

Expression of functional human Epstein-Barr virus/C3d receptor ([CR2] CD21) on insulinoma cell line. Induction of tumor rejection but not diabetes in syngeneic rats

JC Carel, VM Holers, WL Chick, D Littman and PE Lacy
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

We stably expressed human complement receptor 2 ([CR2] CD21 C3d/Epstein-Barr virus [EBV] receptor) on the rat insulinoma cell line RINm5F with a recombinant retroviral vector. CR2-expressing RINm5F cells secreted 78-33% less insulin than parental cells or cells transduced with an antisense vector and could be infected with high-titer EBV. We tested whether human CR2 expression on RINm5F cells would affect tumorigenesis after transplantation to syngeneic New England Deaconess Hospital rats. Non-CR2-expressing antisense-transduced RINm5F cells rapidly grew tumors and caused hypoglycemia, hyperinsulinemia, and the death of the animals after 15.7 +/- 0.7 days. CR2-expressing RINm5F cells were infiltrated by mononuclear cells at an early stage and eventually caused noninfiltrated tumors and the death of the animals after 33.0 +/- 0.4 days. These tumors were CR2- and are believed to have arisen from a minor CR2- population of tumor cells. The pancreatic islets were histologically normal at all time points. We conclude that expression of a xenoantigen on a rat insulinoma cell line induces an immune response in syngeneic rats but does not result in breakage of tolerance to parental or revertant cells.
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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 1991 by the American Diabetes Association.