Differential CMV-Specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection the blood during human
Differential CMV-Specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection the blood during human
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DOI：
10.4049/jimmunol.181.1.546
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
McDyer, John F.
中科院分区：
文献类型：
--
作者：
Pipeling, Matthew R.;West, Erin E.;McDyer, John F.
在肺移植受者（LTRs）原发性巨细胞病毒感染期间获得T细胞反应似乎对宿主防御和同种异体移植物耐久性至关重要，供体(+)/受体（-）（D+R-）个体的死亡率增加。在研究的15例D+R- ltr中，急性原发性巨细胞病毒感染的特征是在存在或不存在肺炎的情况下出现病毒血症，肺气道/同种异体移植物中的病毒载量高于血液。观察到CD8+ T细胞大量涌入肺气道/同种异体移植物，CD4+:CD8+ T细胞比例倒置。与PBMC相比，肺单核细胞对pp65聚合肽的新生CMV（-）特异性CD8+效应频率明显更高，并且在两个区室中主要高于ie1特异性反应和CD4+效应反应。与PBMC相比，肺单核细胞中pp65特异性细胞因子反应的频率显着高于PBMC，并且在原发性感染后，肺气道中CD8+ T细胞长期持续存在效应记忆性收缩。来自PBMC的cmv -四聚体（+）CD(8+) T细胞在病毒血症期间为CD45RA(-)，在分解后转化为CD45RA（+）。相比之下，肺气道/同种异体移植物中cmv特异性CD8+效应物在从急性感染过渡到慢性感染期间保持CD45RA（-）表型。总之，这些数据揭示了急性原发性感染期间，与血液相比，cmv特异性CD8+效应频率、免疫优势和多功能细胞因子反应在肺气道/同种异体移植物中占主导地位。此外，我们还发现，在向慢性感染过渡的过程中，cmv特异性记忆反应在细胞间存在表型差异。
Acquisition of T cell responses during primary CMV infection in lung transplant recipients (LTRs) appear critical for host defense and allograft durability, with increased mortality in donor(+)/recipient(-) (D+R-) individuals. In 15 D+R- LTRs studied, acute primary CMV infection was characterized by viremia in the presence or absence of pneumonitis, with viral loads higher in the lung airways/allograft compared with the blood. A striking influx of CD8+ T cells into the lung airways/allograft was observed, with inversion of the CD4+:CD8+ T cell ratio. De novo CMV(-)specific CD8+ effector frequencies in response to pooled peptides of pp65 were strikingly higher in lung mononuclear cells compared with the PBMC and predominated over IE1-specific responses and CD4+ effector responses in both compartments. The frequencies of pp65-specific cytokine responses were significantly higher in lung mononuclear cells compared with PBMC and demonstrated marked contraction with long-term persistence of effector memory CD8+ T cells in the lung airways following primary infection. CMV-tetramer(+)CD(8+) T cells from PBMC were CD45RA(-) during viremia and transitioned to CD45RA(+) following resolution. In contrast, CMV-specific CD8+ effectors in the lung airways/allograft maintained a CD45RA(-) phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8+ effector frequencies, immunodominance, and polyfunctional cytokine responses predominating in the lung airways/allograft compared with the blood during acute primary infection. Moreover, we show intercompartmental phenotypic differences in CMV-specific memory responses during the transition to chronic infection.