Beta cell apoptosis in T cell-mediated autoimmune diabetes.
Insulin-dependent diabetes mellitus results from T cell-mediated destruction of insulin-producing, pancreatic islet beta cells. How this destruction takes place has remained elusive--largely due to the slow kinetics of disease progression. By crossing a transgenic mouse carrying a beta cell-specific T cell receptor onto the NOD.scid background, we produced a simplified but robust and accelerated model of diabetes. This mouse produces CD4+ T cells bearing transgenic T cell receptor but is devoid of CD8+ T cells and B cells. More importantly, this mouse develops a rapid diabetes, which has allowed us to record and quantify beta cell death. We have determined that beta cells within the inflamed islets die by apoptosis.
Kurrer
M O
MO
Department of Pathology, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Pakala
S V
SV
Hanson
H L
HL
Katz
J D
JD
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D017710:Lymphocyte Transfusion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013997:Time Factors
D016693:Receptors, Antigen, T-Cell, alpha-beta