Regulation of immunities induce by GVHD, HVGD with cytokine abnormalities

众所周知，GVHD和HVGD是免疫疗法移植治疗后的严重并发症，我们最近建立了BMT-GVHD小鼠模型，该模型是通过将亲代骨髓细胞和脾脏细胞作为T细胞来源注射到辐照F1受体中诱导的。我们发现血清IgE和IgG1水平升高与BMT-GVHD相关，如肝脏疾病和脾肿大。BMT-GVHD中IgE水平升高的异型是供体来源的IgE^a，而不是宿主来源的IgE^b。我们还发现，在BMT-GVHD小鼠胸腺中，CD4^+ CD8^+双阳性（DP） T细胞减少，而CD4^+ CD8^-或CD4^- CD8^+单阳性（SP） T细胞增加。经抗il -4抗体（11B11）治疗，可明显降低IgE和IgG1的升高，并可预防肝脏疾病和脾肿大。此外，异常T细胞分化和成熟受到抑制。这些观察结果表明，IL-4在同种异体效应的免疫调节或发病机制中起重要作用，11B11可防止小鼠BMT-GVHD的免疫功能障碍，包括胸腺或脾脏的T细胞分化和自身免疫症状。

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.