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.

用两种鼠巨细胞病毒注射FL混合动力小鼠 （MCMV）或亲本脾细胞（移植物与宿主反应-GVHR） 导致快速和严重的免疫抑制。 接种 选择了病毒或亲本细胞，以便它们 低于严重免疫抑制的阈值。 但是，什么时候 将这两种接种物结合在一起，严重的免疫抑制是 观察到。 此外，用父母注射FL小鼠 仅识别I类MHC决定因素的淋巴细胞没有 导致免疫抑制。 但是，I级的结合 识别和MCMV感染会导致深刻的免疫 抑制。 相反，之间没有可检测的协同作用 II类GVH和MCMV。 在此之前，用MCMV感染宿主小鼠 GVH的诱导导致免疫抑制增强，而 诱导GVH之前，用MCMV感染了供体小鼠 在减少免疫抑制中。 MCMV和GVHR的组合 还导致间质性肺炎 仅对肺部没有可检测到的致病作用。 这些 研究允许研究MCMV的免疫抑制 感染和CMV感染的可能性耦合 用GVHR。 抗病毒药物DHPG抑制病毒 复制，但并不能阻止MCMV与GVH协同作用。 用同性骨髓移植的致命辐照的小鼠发展 辐照后18到24个月之间的肿瘤。 被感染的小鼠 辐照两周后的MCMV没有发展肿瘤。