SYNERGISTIC EFFECTS OF MURINE CYTOMEGALOVIRUS AND GRAFT-VERSUS-HOST REACTION

鼠巨细胞病毒与移植物抗宿主反应的协同效应

• 批准号: 3916407
• 负责人: G M SHEARER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916407
• 关键词: Betaherpesvirinae; Herpesviridae disease; antiviral agents; autologous transplantation; bone marrow transplantation; graft versus host disease; immune response genes; immunosuppression; laboratory mouse; lymphocyte; neoplasm /cancer immunology; radiation immunosuppression; spleen

Injection of Fl hybrid mice with either murine cytomegalovirus (MCMV) or parental spleen cells (graft-versus-host reaction - GVHR) results in rapid and severe immunosuppression. Inoculation of either the virus or parental cells were selected so that they would be below the threshold for severe immunosuppression. However, when these two inocula were combined, severe immunosuppression was observed. Furthermore, injection of Fl mice with parental lymphocytes that recognize only class I MHC determinants does not result in immune suppression. However, a combination of class I recognition and MCMV infection results in profound immune suppression. In contrast, there was no detectable synergy between class II GVH and MCMV. Infection of host mice with MCMV prior to induction of GVH resulted in augmented immune suppression, whereas infection of donor mice with MCMV before induction of GVH resulted in reduced immune suppression. The combination of MCMV and GVHR also resulted in interstitial pneumonitis, whereas either insult alone had no detectable pathogenic effect on the lungs. These studies permit the investigation of the immunosuppression of MCMV infection and the possibility consequences of CMV infection coupled with a GVHR. The anti-viral drug, DHPG, inhibited viral replication but did not prevent MCMV from synergizing with GVH. Lethally irradiated mice grafted with syngeneic bone marrow develop tumors between 18 and 24 months after irradiation. Mice infected with MCMV two weeks after irradiation did not develop tumors.

用鼠巨细胞病毒注射 F1 杂交小鼠 (MCMV) 或亲代脾细胞（移植物抗宿主反应 - GVHR） 导致快速而严重的免疫抑制。 接种 选择病毒或亲本细胞，以便它们 低于严重免疫抑制的阈值。 然而，当 这两种接种物联合使用，会产生严重的免疫抑制 观察到。 此外，Fl小鼠注射亲本 只识别 I 类 MHC 决定簇的淋巴细胞不识别 导致免疫抑制。 然而，I 类的组合 识别和 MCMV 感染导致深度免疫 抑制。 相比之下，两者之间没有可检测到的协同作用。 II 类 GVH 和 MCMV。 实验前用 MCMV 感染宿主小鼠 GVH 的诱导导致免疫抑制增强，而 在诱导 GVH 之前用 MCMV 感染供体小鼠 减少免疫抑制。 MCMV和GVHR的结合 也导致间质性肺炎，而任何一种侮辱 单独使用对肺部没有可检测到的致病作用。 这些 研究允许调查 MCMV 的免疫抑制作用 感染和巨细胞病毒感染的可能后果 具有 GVHR。 抗病毒药物DHPG可抑制病毒 复制但不阻止 MCMV 与 GVH 协同作用。 接受致命辐射的小鼠移植同基因骨髓后发育 照射后 18 至 24 个月内的肿瘤。 老鼠被感染 用MCMV照射两周后没有形成肿瘤。