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

注射小鼠巨细胞病毒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是为了让它们 低于严重免疫抑制的门槛。但是，当 这两种疫苗联合接种，出现了严重的免疫抑制 观察到的。此外，给F1小鼠注射亲本 只识别I类MHC决定簇的淋巴细胞不能识别 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 压制。相反，两者之间没有明显的协同作用。 第二类GVH和MCMV。MCMV感染前宿主小鼠的研究 诱导GVH导致免疫抑制增强，而 供体小鼠在GVH诱导前感染MCMV的研究 减少免疫抑制。MCMV与GVHR的结合 也会导致间质性肺炎，而无论是侮辱 单独使用对肺部没有明显的致病作用。这些 研究允许调查MCMV的免疫抑制作用 感染与巨细胞病毒感染的可能后果耦合 带着GVHR。抗病毒药物DHPG抑制病毒 复制，但并未阻止MCMV与GVH的协同作用。 经致死照射后移植同基因骨髓的小鼠 肿瘤发生在照射后18至24个月。感染的小鼠 MCMV照射后两周未发生肿瘤。

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.