Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantation. The IgE allotype is an important marker of graft-versus-host disease.
Induction of a graft-vs-host reaction in irradiated (BALB/c X C57BL/6)F1 mice (CBF1 mice) with bone marrow cells (BMC) plus spleen cells of BALB/c mice leads to bone marrow transplantation--GVHD (BMT-GVHD). BMT-GVHD is characterized by liver disease, splenomegaly, and hypergammopathy. In addition, we found that increased serum IgE and IgG1 levels were correlated with BMT-GVHD such as liver disease and splenomegaly. The allotype of increased IgE levels in BMT-GVHD was IgEa of donor origin, not IgEb of host origin. We also found that in the thymus of murine BMT-GVHD, the CD4+ CD8+ double-positive T cells were decreased, but the CD4+ CD8- or CD4- CD8+ single-positive T cells were increased. Interestingly, double-positive T cells appeared in the spleen, suggesting that abnormal T cell differentiation existed in murine BMT-GVHD. When the recipients were treated with anti-IL-4 Ab (11B11), the increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell differentiation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of allogeneic effects, and 11B11 prevents immunodysfunction including T cell differentiation in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.
Ushiyama
C
C
Division of Rheumatology, Juntendo University, School of Medicine, Tokyo, Japan.
Hirano
T
T
Miyajima
H
H
Okumura
K
K
Ovary
Z
Z
Hashimoto
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control*; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus / Q000276:immunology; D013154:Spleen / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology; D015430:Weight Gain / Q000276:immunology
D000911:Antibodies, Monoclonal; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E