IL-10 is necessary and sufficient for autoimmune diabetes in conjunction with NOD MHC homozygosity.
Contrary to expectations based on in vitro experiments, we previously found that pancreatic IL-10 did not inhibit autoimmune diabetes but accelerated it in an MHC-dependent manner. Therefore, the ability of IL-10 to overcome the absence of all non-MHC diabetes susceptibility (Idd) alleles was studied in transgenic mice expressing pancreatic IL-10 backcrossed to B10.H2g7 congenic mice, which have no Idd alleles other than NOD MHC (H2g7). IL-10 transgenic backcross 1 (BC1) mice with H2g7/g7 haplotype developed clear-cut insulitis and diabetes, but neither transgenic mice with the H2g/b haplotype nor nontransgenic BC1 mice did so. Further implicating IL-10 in autoimmune diabetes, anti-IL-10 antibody treatment inhibited the development of insulitis in NOD mice. These results suggest that IL-10 may be necessary and sufficient for producing autoimmune diabetes in conjunction with NOD MHC homozygosity and that some Idd genes may be related to the regulation of IL-10.
Lee
M S
MS
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Mueller
R
R
Wicker
L S
LS
Peterson
L B
LB
Sarvetnick
N
N
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006720:Homozygote; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10