Müller C A, Hebart H, Roos A, Roos H, Steidle M, Einsele H
Abteilung II mit Sektion für Transplantationsimmunologie und Immunhämatologie, Universität Tübingen, Germany.
Med Microbiol Immunol. 1995 Oct;184(3):115-21. doi: 10.1007/BF00224347.
In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune response and, thus, provoke the immunopathology of IP.
在一项回顾性分析中，对30例连续的同种异体骨髓移植受者的肺活检标本进行了研究，这些受者均已死亡，其中18例死于间质性肺炎（IP），12例死于其他各种原因。通过培养、原位杂交、聚合酶链反应（PCR）以及针对人巨细胞病毒（HCMV）蛋白的免疫组织化学方法，检测肺组织中HCMV的局部存在情况。发现所有患有IP的患者在肺活检中HCMV均呈阳性。PCR在肺活检中对HCMV检测的灵敏度最高，但在18份PCR阳性样本中的15份中，至少可通过一种其他技术确认局部HCMV感染。在应用的所有技术检测中，从12例无IP的患者获取的所有肺活检标本中，除1例在PCR检测中有微弱的HCMV - DNA信号外，其余均为HCMV阴性。肺组织中临床、组织学及免疫组织学改变的严重程度与活检中检测到的HCMV - DNA量或HCMV阳性细胞数量无关。肺泡上皮细胞上HLA - II类抗原及细胞间黏附分子-1（ICAM - 1）表达增加，以及仅在HCMV阳性肺活检标本中有活化的CD8 +或CD4 +淋巴细胞浸润，表明T细胞介导的免疫反应参与了IP的发病机制。由于所有分析的患者均出现严重的急性或广泛的慢性移植物抗宿主病（GvHD），但只有那些发生肺部HCMV感染的患者发展为IP，因此HCMV的播散似乎是IP发生的首要条件。然而，GvHD可能会干扰随后抗病毒免疫反应的正常控制，从而引发IP的免疫病理学改变。
