Effect of T-cell receptor V beta-specific monoclonal antibodies on cyclophosphamide-induced diabetes mellitus in non-obese diabetic mice.
The expression of specific T-cell receptor gene segments by T lymphocytes appears to be critically important for the induction of several experimental autoimmune diseases mediated by these cells. We examined whether this situation also applied to non-obese diabetic mice by using various T-cell receptor V beta-specific monoclonal antibodies. No significant age- or sex-related differences were observed in V beta usage by peripheral and splenic T lymphocytes. CD8+ T lymphocytes among the islet-derived mononuclear cells isolated from 20-week-old female non-obese diabetic mice showed heterogeneity of their V beta gene usage. In order to examine the role of T lymphocyte subsets expressing specific T-cell receptor V beta segments in the development of diabetes mellitus, T-cell receptor V beta-specific monoclonal antibodies were administered to 10-week-old male non-obese diabetic mice treated with cyclophosphamide. None of the antibodies used could significantly diminish the incidence of cyclophosphamide-induced diabetes and the severity of insulitis [anti-V beta 3 (11 of 22 mice became diabetic, 50%), anti-V beta 5 (9 of 14, 64%), anti-V beta 8 (9 of 21, 43%), anti-V beta 11 (12 of 23, 52%), anti-V beta 14 (7 of 12, 58%), and anti-V beta 5 + anti-V beta 11 (6 of 12, 50%)] when compared with control mice (12 of 21, 57%). In addition, there were no significant differences in T-cell receptor V beta usage between diabetic and non-diabetic cyclophosphamide-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Taki
T
T
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yokono
K
K
Amano
K
K
Hatamori
N
N
Hirao
Y
Y
Tominaga
Y
Y
Maeda
S
S
Kasuga
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000633:toxicity*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D016688:Mice, Inbred NOD / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide