Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb.
Diverse adhesion molecules participate in many important responses and thus would be implicated in the pathogenesis of various autoimmune diseases. However, there is little evidence for the role of these molecules in autoimmune insulin-dependent diabetes mellitus. Here we present several lines of evidence suggesting that leukocyte function-associated antigen-1 (LFA-1) and its counter-receptor intercellular adhesion molecules (ICAM-1), one of the most important pairs among these adhesion molecules, are involved in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Immunohistochemical study showed the hyperexpression of ICAM-1 on islet-infiltrating mononuclear cells and vascular endothelium in NOD pancreas. In vivo administration of anti-LFA-1 or anti-ICAM-1 mAb from 5 to 30 (or 12) weeks of age exerted a very strong preventative effect on the development of spontaneous diabetes with a marked reduction of insulitis, whereas both antibodies, even combined to use simultaneously, could not prevent cyclophosphamide-induced diabetes. Adoptive transfer of insulitis and diabetes to young NOD mice following the injection of islet-derived mononuclear cells from diabetic donors was completely blocked by administration of both antibodies to recipients. The present study, therefore, provides the first evidence that immunointervention to LFA-1-ICAM-1 interaction has a strong prophylactic effect on autoimmune diabetes in NOD mice.
Hasegawa
Y
Y
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yokono
K
K
Taki
T
T
Amano
K
K
Tominaga
Y
Y
Yoneda
R
R
Yagi
N
N
Maeda
S
S
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D003520:Cyclophosphamide