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

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:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
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中文摘要
翻译
给F1杂交小鼠注射鼠巨细胞病毒 (MCMV)或亲本脾细胞(移植物抗宿主反应- GVHR) 导致快速和严重的免疫抑制。 接种 选择病毒或亲本细胞, 低于严重免疫抑制的阈值 然而当 将这两种接种物联合使用, 观察 此外,注射亲本F1小鼠, 仅识别I类MHC决定簇的淋巴细胞 导致免疫抑制。 然而,I类的组合 识别和MCMV感染导致深刻的免疫 镇压 相比之下,没有检测到的协同作用, II类GVH和MCMV。 在接种前用MCMV感染宿主小鼠 GVH的诱导导致增强的免疫抑制,而 在诱导GVH之前用MCMV感染供体小鼠, 减少免疫抑制。 MCMV和GVHR的联合应用 也导致间质性肺炎,而无论是损伤 单独使用对肺部没有可检测到的致病作用。 这些 研究允许对MCMV的免疫抑制进行调查 感染和CMV感染的可能后果 一个GVHR。 抗病毒药物DHPG抑制了病毒 复制,但不能阻止MCMV与GVH的协同作用。 致死性辐射小鼠移植同基因骨髓发育 肿瘤在照射后18至24个月。 感染小鼠 照射后两周用MCMV治疗没有发生肿瘤。
英文摘要
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.
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SYNERGISTIC EFFECTS OF MURINE CYTOMEGALOVIRUS AND GRAFT-VERSUS-HOST REACTION