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- Title
Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice.
- Authors
Fujihira, Kazuhiro; Nagata, Masao; Fujihira, K; Nagata, M; Moriyama, H; Yasuda, H; Arisawa, K; Nakayama, M; Maeda, S; Kasuga, M; Okumura, K; Yagita, H; Yokono, K
- Abstract
A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Thl cell differentiation. When C17.8 was administered from 5 to 30 weeks of age, NOD mice exhibited suppression of both insulitis and diabetes. However, when C17.8 administration ceased at 15 weeks of age, 8 of 13 recipients showed diabetes at 30 weeks of age. These results suggest that IL-12 plays an important role not only in the development of effector cells but also in their activation. In contrast, when C17.8 was injected into 2-week-old female NOD mice for 6 consecutive days, all 16 recipients showed diabetes at 30 weeks of age, whereas 12 of 20 control mice became diabetic. This result suggests that depletion of endogenous IL-12 at a young age results in the enhancement of diabetes. Flow cytometric analysis indicated that activated memory T-cells were present in higher numbers after C17.8 treatment. Transfer of spleen cells from 15-week-old C17.8-treated NOD mice to NOD-scid mice resulted in an earlier onset and a higher incidence of diabetes. Furthermore, administration of C17.8 to 2-week-old NOD mice also resulted in a much earlier onset of diabetes. These results suggest that short-term treatment with anti-IL-12 antibody prohibits IL-2 production at a young age, which may influence the expansion and apoptosis of pathogenic T-cells, resulting in the acceleration of autoimmune diabetes.
- Subjects
JAPAN; KOBE-shi (Japan); IMMUNOSUPPRESSION; AUTOIMMUNE diseases; DIABETES; INTERLEUKIN-12
- Publication
Diabetes, 2000, Vol 49, Issue 12, p1998
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.49.12.1998