Prevention of insulitis and diabetes in beta 2-microglobulin-deficient non-obese diabetic mice.
beta 2-Microglobulin (beta 2m)-deficient non-obese diabetic (NOD) mice were established by crossing beta 2m-deficient 129/Sv mice with NOD mice, and used to examine the possible involvement of MHC class I molecules and CD8+ T cells in the development of insulitis and diabetes. In these mice, MHC class I molecules were not expressed, resulting in no generation of CD8+ T cells. None of eight lines of beta 2m-deficient NOD mice (-/-) established developed overt diabetes by 32 weeks, while control littermates (+/+) became diabetic by 22 weeks. histological studies showed no significant lymphocyte infiltration of the islets (insulitis score: 0.03 +/- 0.03) in any of the beta 2m-deficient NOD mice (-/-) compared with littermate NOD mice (+/+) with overt insulitis (1.42 +/- 0.28). These findings support the notion that the expression of MHC class I molecules and/or CD8+ T cells plays an essential role in the infiltration of CD4+ T cells in islets as well as the development of diabetes in NOD mice.
Sumida
T
T
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Furukawa
M
M
Sakamoto
A
A
Namekawa
T
T
Maeda
T
T
Zijlstra
M
M
Iwamoto
I
I
Koike
T
T
Yoshida
S
S
Tomioka
H
H
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010182:Pancreatic Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin