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) F-1 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 hypergammop athy. In addition, we found that increased serum IgE and IgG1 levels w ere correlated with BMT-GVHD such as liver disease and splenomegaly. T he allotype of increased IgE levels in BMT-GVHD was IgE(a) of donor or igin, not IgE(b) of host origin. We also found that in the thymus of m urine BMT-GVHD, the CD4(+)CD8(+) double-positive T cells were decrease d, but the CD4(+)CD8(-) or CD4(-)CD8(+) single-positive T cells were i ncreased. interestingly, double-positive T cells appeared in the splee n, suggesting that abnormal T cell differentiation existed in murine B MT-GVHD. When the recipients were treated with anti-IL-4 Ab (11B11), t he increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell different iation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of a llogeneic effects, and 11B11 prevents immunodysfunction including T ce ll differentiation in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.