IMMUNE REGULATION OF MURINE GRAFT-VERSUS-HOST DISEASE

移植物抗宿主病是一种常见的疾病。 在骨髓移植之后。尽管使用了大调 组织相容性复合体(MHC)相合的骨髓供者 移植后的免疫抑制方案，大 仍有许多患者出现移植物抗宿主病。这些发现表明 认为非MHC基因座在调节和 GVHD的诱导。这些研究的目标是描述 非MHC基因座对调控和 诱导小鼠移植物抗宿主病。这些研究将使用小鼠模型 静脉注射诱发慢性移植物抗宿主病 DBA/2脾细胞注射未照射(C57BL/6x) DBA/2)F1小鼠同时注射来自对方的脾细胞 亲本株C57BL/6可导致急性移植物抗宿主病。.的存在 急性白血病患者体内溶细胞T淋巴细胞及其抑制细胞的研究 但慢性形式的移植物抗宿主病是一些与众不同的 两种形式的移植物抗宿主病的特点。这些差异 已被证明受非MHC基因座调控。初步 使用BXD重组近交系的实验证明 一个或多个推定的位置，绘制大约10个地图单元的远端 7号染色体上调节体内CTL产生的Hbb。 回交实验将试图量化 控制每个GVHD特征的基因座，并更精确地映射 7号染色体上的一个或多个基因座。其他实验将 确定B6和DBA/2等位基因的菌株分布 调节体内CTL的产生，并将检测是否存在一个或多个基因座 调节CTL作为乘客基因座在 H-1或Hbb同源菌株的产生。进一步的实验 将尝试定义收件人的特征和 导致DBA/2脾功能不全的供体细胞 B6D2F1体内注射细胞产生CTL的研究 收件人。CTL前兆频率分析将进行 验证发现DBA/2 CTL前体正在 被消灭而不是被压制。因为30-40个脾细胞 周龄DBA/2小鼠在体内的反应与来自 6-8周龄的小鼠，这些差异将被研究以确定 供体细胞在体内反应中的作用。

Graft-versus-host disease (GVHD) is a common occurrence following bone marrow transplantation. Despite the use of major histocompatibility complex (MHC)-matched bone marrow donors and immunosuppression regimens following transplant, large numbers of patients still develop GVHD. These findings indicate that non-MHC loci play an important role in the regulation and induction of GVHD. The goal of these studies is to characterize non-MHC loci which are important for the regulation and induction of murine GVHD. These studies will use a murine model of GVHD in which chronic GVHD is induced by intravenous injection of DBA/2 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 mice while injection of spleen cells from the other parental strain, C57BL/6, results in acute GVHD. The presence of in vivo cytolytic T lymphocytes and suppressor cells in the acute form but the chronic form of GVHD are some of the distinguishing characteristics of the two forms of GVHD. These differences have been shown to be regulated by non-MHC loci. Preliminary experiments using BXD recombinant inbred strains have identified a putative locus or loci mapping approximately 10 map units distal to Hbb on chromosome 7 that regulates in vivo CTL production. Backcross experiments will attempt to quantitate the number of loci that regulate each GVHD trait and to more precisely map the locus or loci on chromosome 7. Additional experiments will determine the strain distribution of the B6 and DBA/2 alleles regulating in vivo CTL production and will test if the locus or loci regulating CTL were transferred as passenger loci during the production of H-1 or Hbb congenic strains. Further experiments will attempt to define the characteristics of the recipient and donor cells which contribute to the inability of the DBA/2 spleen cells to generate in vivo CTL when injected into B6D2F1 recipients. CTL precursor frequency analysis will be done to verify the finding that DBA/2 CTL precursors are being eliminated and not suppressed. Because spleen cells from 30-40 week old DBA/2 mice respond differently in vivo than cells from 6-8 week old mice, these differences will be studied to determine the donor cells' role in the in vivo response.