Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.
Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.
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DOI：
10.1016/j.trim.2014.10.005
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发表时间：
2015-01
影响因子：
1.5
通讯作者：
Palmer SM
中科院分区：
文献类型：
--
作者：
Gowdy KM;Martinu T;Nugent JL;Manzo ND;Zhang HL;Kelly FL;Holtzman MJ;Palmer SM
骨髓移植（BMT）接受者经历频繁和严重的呼吸道病毒感染（RVI）。然而，易患RVIs的免疫机制尚不确定。因此，我们假设抗病毒T细胞免疫受损作为同种异体BMT的结果，独立于药理学免疫抑制，并负责增加对RVI的易感性。将来自C57 BL/6（H2 b）小鼠的骨髓和脾细胞移植到B10.BR（H2k）（Allo）或C57 BL/6（H2 b）（Syn）受体中。移植后5周，这些小鼠鼻内接种小鼠副流感病毒1型（mPIV-1），通常称为仙台病毒（SeV），并监测相关的免疫学和疾病终点。严重和持续的气道炎症，上皮损伤，并增加死亡率后，发现病毒感染的Allo小鼠，但没有在对照Syn和非移植小鼠。此外，病毒清除在Allo小鼠中延迟，如通过在接种后（p.i.）但在对照小鼠中则不然。与这些事件一致，我们还在感染后第8天在Allo小鼠的肺中检测到总的和病毒特异性的CD 8 + T细胞水平降低，以及抑制性受体程序性死亡-1（PD-1）的T细胞表达增加。在感染后第8天，将来自从SeV感染恢复的非移植小鼠的CD 8 + T细胞连续转移到Allo小鼠中。恢复正常水平的病毒清除，上皮修复和肺部炎症。综上所述，这些结果表明，同种异体BMT导致更严重的RVI，这是基于未能产生适当的肺部CD 8 + T细胞应答，这为改善BMT后RVI的结局提供了重要的潜在靶机制。
Bone marrow transplant (BMT) recipients experience frequent and severe respiratory viral infections (RVI). However, the immunological mechanisms predisposing to RVIs are uncertain. Therefore, we hypothesized that antiviral T cell immunity is impaired as a consequence of allogeneic BMT, independent of pharmacologic immunosuppression, and is responsible for increased susceptibility to RVI. Bone marrow and splenocytes from C57BL/6(H2b) mice were transplanted into B10.BR(H2k) (Allo) or C57BL/6(H2b) (Syn) recipients. Five weeks after transplantation, these mice were inoculated intranasally with mouse parainfluenza virus type 1 (mPIV-1), commonly known as Sendai virus (SeV), and monitored for relevant immunological and disease endpoints. Severe and persistent airway inflammation, epithelial injury, and enhanced mortality are found after viral infection in Allo mice but not in control Syn and non-transplanted mice. In addition, viral clearance is delayed in Allo mice as evidenced by prolonged detection of viral transcripts at Day 15 post-inoculation (p.i.) but not in control mice. In concert with these events, we also detected decreased levels of total and virus-specific CD8+ T cells, as well as increased T cell-expression of inhibitory receptor programmed death-1 (PD-1), in the lungs of Allo mice at Day 8 p.i. Adoptive transfer of CD8+ T cells from non-transplanted mice recovered from SeV infection into Allo mice at Day 8 p.i. restored normal levels of viral clearance, epithelial repair and lung inflammation. Taken together these results indicate that allogeneic BMT results in more severe RVI based on the failure to develop an appropriate pulmonary CD8+ T cell response, providing an important potential mechanism to target in improving outcomes of RVI after BMT.
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