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.
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.
Carel
J C
JC
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Holers
V M
VM
Chick
W L
WL
Littman
D
D
Lacy
P E
PE
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005822:Genetic Vectors; D006084:Graft Rejection; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000276:immunology / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011951:Receptors, Complement / Q000235:genetics / Q000502:physiology*; D017464:Receptors, Complement 3d; D014162:Transfection; D014185:Transplantation, Isogeneic
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001786:Blood Glucose; D007328:Insulin; D011951:Receptors, Complement; D017464:Receptors, Complement 3d