Increased IgE level as a marker of host-versus-graft disease: inhibition of this HVGD with a monoclonal antibody to IL-4.
BALB/c mice injected at birth with (BALB/c x C57BL/6)F1 hybrid spleen cells developed host versus graft disease (HVGD) with immunological features, such as various autoantibodies, immune complex nephritis, hepatosplenomegaly, and malignant lymphomas. In addition we found that the increased IgE levels correlated strongly with the histological grades or stages of the liver disease. In the sera of mice with HVGD and liver alterations, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were detected. The subclass of ASMA was IgG1, whereas the subclasses of ANA were IgG1, IgG2a, and IgG2b. When the recipient BALB/c mice were injected at birth and at Day 3 in addition also with monoclonal anti-IL-4 antibody 11B11, the increase of IgE and IgG1 was markedly reduced and the liver disease was drastically prevented. These observations suggest that IL-4 plays an important role in the initiation of the immunoregulatory function or pathogenesis of the allogeneic effects and that the monoclonal anti-IL-4 antibody 11B11 prevents the immunodysfunctions and the autoimmune hepatopathy in mice with HVGD. The increased IgE level in the serum is a good marker of HVGD.
Division of Rheumatology and Internal Medicine, Juntendo University, School of Medicine, Tokyo, Japan.
S
S
Takai
M
M
Tateno
T
T
Hirano
N
N
Kondo
S
S
Hirose
T
T
Yoshiki
D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006789:Host vs Graft Reaction; D007073:Immunoglobulin E / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology*; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009130:Muscle, Smooth / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E