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
Ushiyama, C.; Hirano, T.; Miyajima, H.; Okumura, K.; Ovary, Z.; Hashimoto, H.
Journal of Immunology 154(6): 2687-2696
1995
ISSN/ISBN: 0022-1767 PMID: 7876541 Document Number: 453859
Induction of a graft-vs-host reaction in irradiated (BALB/c times C57BL/6)F-1 mice (CBF, 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 IgE-a of donor origin, not IgE-b 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.