Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma.
The NOD mouse is studied as an animal model of human insulin-dependent diabetes mellitus (IDDM). To evaluate the role of IFN gamma in the pathogenesis of the disease, we have studied the effect of anti-IFN gamma mAb on the expression of insulitis and clinical diabetes. Treatment of mice with anti-IFN gamma mAb prevented the induction of early IDDM by cyclophosphamide as well as the adoptive transfer of diabetes by spleen cells from diabetic NOD mice. The protection against induction of diabetes by cyclophosphamide was observed in animals treated with the anti-IFN gamma mAb within 24 h following the first cyclophosphamide injection but not in animals in which mAb treatment was started 7 days later. Transfer of disease was prevented both in adult irradiated and in newborn recipients. The absence of clinical signs in these mice was corroborated by a significant reduction of both the extent and severity of insulitis. Over-expression of Ia antigen on endothelial cells lining the islets was also considerably reduced in mice treated with mAb. These data strongly suggest a role for IFN gamma during the autoimmune process leading to beta cell destruction in diabetes and prompt further investigation of the use of such antibodies in the immunoprevention of IDDM.
Debray-Sachs
M
M
INSERM U25, CNRS UA122, Hôpital Necker, Paris, France.
Carnaud
C
C
Boitard
C
C
Cohen
H
H
Gresser
I
I
Bedossa
P
P
Bach
J F
JF
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003520:Cyclophosphamide / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D004727:Endothelium / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology* / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D051381:Rats; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007371:Interferon-gamma; D003520:Cyclophosphamide