Suppression of T(h)1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10.
Insulin-dependent diabetes mellitus in the NOD mouse model is caused by the T cell-mediated autoimmune destruction of pancreatic beta cells. Viral IL-10 (vIL-10), encoded in the Epstein-Barr virus genome, shares many of the anti-inflammatory properties of cellular IL-10, but lacks its immunostimulatory properties. In the present study, we generated transgenic (Tg) NOD mice in which vIL-10 was produced exclusively in pancreatic islets and investigated the effect of vIL-10 on the development of diabetes. The accumulation of lymphocytes around islets was more prominent, but the invasive insulitis decreased in the vIL-10 Tg mice. The incidence of diabetes was markedly reduced in the vIL-10 Tg mice, in clear contrast to the accelerated diabetes seen in the murine IL-10 Tg NOD mice. IL-12p40 and IFN-gamma mRNA levels were decreased in pancreata of the vIL-10 Tg mice, although CD4 mRNA level was markedly increased. These results suggest that locally produced vIL-10 induced leukocyte migration, but inhibited the activation of T(h)1, probably through suppressing the production of IL-12. They indicate that vIL-10 may well be superior to cellular IL-10 in the treatment of autoimmune diabetes. The vIL-10 Tg NOD mice should provide a useful tool for understanding the differential action of vIL-10 versus cellular IL-10.
Kawamoto
S
S
Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
Nitta
Y
Y
Tashiro
F
F
Nakano
A
A
Yamato
E
E
Tahara
H
H
Tabayashi
K
K
Miyazaki
J
J
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
D015704:CD4 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma