Induction of autoimmune disease by graft-versus-host reaction across MHC class II difference: modification of the lesions in IL-6 transgenic mice.
We examined the effect of IL-6 on the development of autoimmune diseases (primary biliary cirrhosis, Sjögren's syndrome) employing murine graft-versus-host reaction (GVHR) model with MHC class II disparity. For this purpose, we used IL-6 transgenic (B6.6) mice in which a high level of IL-6 was detected. C57Bl/6 (B6) spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice ((bm12 x B6.6)F1) and GVHR with MHC class II disparity was induced. The transgenic hybrid mice with GVHR showed a larger spleen index and contained a higher serum level of IL-6 than those without GVHR. Autoimmune-like lesions in transgenic recipients became weakened compared with those in non-transgenic (bm12 x B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12 x B6.6)F1 GVHR group were significantly higher than that of (bm12 x B6)F1 GVHR group. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases.
Kimura
T
T
Animal Centre for Biomedical Research, Faculty of Medicine, University of Tokyo, Japan.
Suzuki
K
K
Inada
S
S
Hayashi
A
A
Saito
H
H
Miyai
T
T
Ohsugi
Y
Y
Matsuzaki
Y
Y
Tanaka
N
N
Osuga
T
T
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D006087:Graft vs Host Reaction / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology; D010179:Pancreas / Q000473:pathology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology; D012469:Salivary Glands / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology
D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D011768:Pyruvate Dehydrogenase Complex