Induction of peri-insulitis but not diabetes in islet transplants expressing a single foreign antigen. A multi-stage model of disease.
We have created a new transgenic model in which the human Epstein-Barr virus receptor, CR2 (CD21), has been expressed in pancreatic beta-cells. Mice derived from three transgenic founders bred into H-2b (C57BL/6) or H-2k (CBA) genetic backgrounds did not become spontaneously diabetic. After transplantation of CR2-expressing islets under the kidney capsule of genetically matched recipients, a histologic picture of peri-insulitis was found. However, animals did not manifest cellular invasion of the islets, destruction of the islets, or diabetes for at least 230 days. Significant numbers of both T and B lymphocytes were found in the cell population surrounding the islets. A pronounced serologic response to CR2 was also present and appeared to precede the onset of peri-insulitis. Thus, in this model, we have separated the process of diabetes induction into at least two phases. One is associated with peri-islet infiltration and an antibody response. However, at least one second signal is likely necessary for the process of islet destruction to follow.
Holers
V M
VM
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
Hollis
G F
GF
Schwartz
B D
BD
Evans
R J
RJ
Strauss-Schoenberger
J
J
Carel
J C
JC
Barney
D L
DL
Li
B
B
Stafford-Hollis
J
J
Lacy
P E
PE
D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology*
D017464:Receptors, Complement 3d