CLEARANCE OF SENDAI VIRUS BY CD8(+) T-CELLS REQUIRES DIRECT TARGETING TO VIRUS-INFECTED EPITHELIUM
CLEARANCE OF SENDAI VIRUS BY CD8(+) T-CELLS REQUIRES DIRECT TARGETING TO VIRUS-INFECTED EPITHELIUM
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DOI：
10.1002/eji.1830250120
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发表时间：
1995-01-01
影响因子：
5.4
通讯作者：
DOHERTY, PC
中科院分区：
文献类型：
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作者：
HOU, S;DOHERTY, PC
在从仙台病毒感染的小鼠中回收的支气管肺泡灌洗（BAL）群体中发现了极少量的CD 8（+）T细胞，这些小鼠是β 2-微球蛋白（β 2-m）基因破坏的纯合（-/-）。在使用基本上I类主要组织相容性复合体（MHC）糖蛋白阴性的β 2-m（-/-）受体和正常β 2-m（+/+）骨髓制备的8-12周放射嵌合体的肺炎肺中，CD 8（+）集的患病率显著增加。即使如此，CD 8（+）（而不是CD 4（+））淋巴细胞计数仍然比（+/+）-->（+/+）对照组低得多。（+/+）-->（+/+）和（+/+）-->（-/-）嵌合体可清除仙台病毒，并在两组的BAL中均发现了对H-2K（B）+病毒核蛋白肽具有特异性的病毒免疫CD 8（+）细胞毒性T淋巴细胞（CTL）。然而，在体内耗尽CD 4（+）群体后，只有（+/+）->（+/+）小鼠能够处理感染。类似地，过继转移的H-2K（B）限制性CD 8（+）T细胞来自先前致敏的（+/+）小鼠，也不能从骨髓重建2周内感染的（+/+）-->（-/-）嵌合体的肺中清除病毒，尽管它们在（+/+）-->（+/+）对照中有效。因此，仙台病毒免疫CD 8（+）T细胞不能消除病毒感染的β 2-m（-/-）肺上皮细胞，这些细胞可能被认为表达非常少量的分离的I类重链或I类MHC糖蛋白，该糖蛋白已结合来源于肺炎肺中存在的β 2-m（+/+）T细胞或巨噬细胞的β 2-m。此外，在BAL群体中暴露于β 2-m（+/+）刺激物的CD 8（+）CTL不能以某种旁观者模式操作以从呼吸道上皮清除病毒。
Minimal numbers of CD8(+) T cells are found in bronchoalveolar lavage (BAL) populations recovered from Sendai virus-infected mice that are homozygous (-/-) for a beta 2-microglobulin (beta 2-m) gene disruption. The prevalence of the CD8(+) set was substantially increased in the pneumonic lungs of 8-12-week radiation chimeras made using substantially class I major histocompatibility complex (MHC) glycoprotein-negative beta 2-m (-/-) recipients and normal beta 2-m (+/+) bone marrow. Even so, the CD8(+) (but not the CD4(+)) lymphocyte counts were still much lower than in the (+/+)-->(+/+) controls. The (+/+)-->(+/+) and (+/+)-->(-/-) chimeras cleared Sendai virus and potent virus-immune CD8(+) cytotoxic T lymphocytes (CTL) specific for H-2K(b) + viral nucleoprotein peptide were found in the BAL from both groups. However, following irt vivo depletion of the CD4(+) population, only the (+/+)-->(+/+) mice were able to deal with the infection. Similarly, adoptively transferred, H-2K(b)-restricted CD8(+) T cells from previously-primed (+/+) mice also failed to clear virus from the lungs of (+/+)-->(-/-) chimeras infected within 2 weeks of reconstitution with bone marrow, though they were effective in the (+/+)-->(+/+) controls. Sendai virus-immune CD8(+) T cells are thus unable to eliminate virus-infected beta 2-m (-/-) lung epithelial cells that might be thought to be expressing very small amounts of either isolated class I heavy chain, or class I MHC glycoprotein that has bound beta 2-m derived from beta 2-m (+/+) T cells or macrophages present in the pneumonic lung. Furthermore, the CD8(+) CTL that are being exposed to beta 2-m (+/+) stimulators in the BAL population cannot operate in some bystander mode to clear virus from respiratory epithelium.