Regulation of immunities induce by GVHD, HVGD with cytokine abnormalities

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It is well known that GVHD and HVGD are severe complications after transplantation tharapy for immunotherapies, we recently established a murine model of BMT-GVHD that was induced by the injection of parental bone marrow cells plus spleen cells as a source of T cells into irradiated F1 recipients.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 (DP) T cells were decreased, but the CD4^+ CD8^- or CD4^- CD8^+ single positive (SP) T cells were increased. When the recipients were treated with anti-IL-4 antibody (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 differentiaiton in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.