Anti-asialo GM1 antibody suppression of cyclophosphamide-induced diabetes in NOD mice.
To elucidate the role of natural killer (NK) cells in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse, we examined whether or not cyclophosphamide-induced diabetes occurs in NOD mice intraperitoneally (i.p.) injected with anti-asialo GM1 antibody. Two weeks after a single intraperitoneal injection of cyclophosphamide, none of the 24 NOD mice which had previously been treated with antiasialo GM1 antibody, 2-3 times per week for either 2 or 3 weeks, had developed indications of diabetes such as glycosuria or a high plasma glucose level. On the other hand, signs of diabetes were found in 10 of 24 control NOD mice injected with normal rabbit Ig instead of anti-asialo GM1 antibody (p less than 0.01). The NK cell activities of spleen cells from anti-asialo GM1 antibody-treated mice were significantly lower than those of control mice (p less than 0.01). Flowcytometry analysis demonstrated that anti-asialo GM1 antibody-positive cells had disappeared from the spleens of anti-asialo GM1 antibody-injected mice but no suppression of CD8+ and CD4+ cells could be demonstrated. These observations suggest that NK cells are involved in the development of diabetes in NOD mice.
Maruyama
T
T
Department of Medicine, Social Insurance Saitama Chuo Hospital, Japan.
Watanabe
K
K
Takei
I
I
Kasuga
A
A
Shimada
A
A
Yanagawa
T
T
Kasatani
T
T
Suzuki
Y
Y
Kataoka
K
K
Saruta
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D001786:Blood Glucose; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003520:Cyclophosphamide