Comparison of cytotoxic T lymphocyte efficacy in acute and persistent lymphocytic choriomeningitis virus infection
Comparison of cytotoxic T lymphocyte efficacy in acute and persistent lymphocytic choriomeningitis virus infection
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DOI：
10.1098/rspb.2011.0453
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发表时间：
2011-11-22
影响因子：
4.7
通讯作者：
Regoes, Roland R.
中科院分区：
文献类型：
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作者：
Graw, Frederik;Richter, Kirsten;Regoes, Roland R.
细胞毒性T淋巴细胞(CTL)介导的免疫反应在持续性感染中经常被发现是功能受损的。据推测，这种损害有助于感染的持久性。在这项研究中，我们用体内CTL杀伤试验比较了CD8(+)T细胞反应在急性和持续感染淋巴细胞性脉络膜脑膜炎病毒小鼠中的杀伤效果。为了推断CTL的杀伤效果，我们开发了一个新的数学模型，描述了小鼠血液中多肽脉冲细胞随着时间的推移而消失的过程。我们估计，在急性感染中，多肽脉冲细胞的半衰期低于持续感染，这表明CD8(+)T细胞反应在急性感染中具有更高的杀伤力。然而，通过控制急性和持续感染小鼠中不同水平的CTL，我们发现持续感染中的CTL仅比急性感染中的CTL效果低两倍。这些结果有力地表明，持续感染中CD8(+)T细胞的体内细胞毒作用是通过CTL的数量而不是它们的个体功能来调节的。
Immune responses mediated by cytotoxic T lymphocytes (CTLs) have often been found to be functionally impaired in persistent infections. It is assumed that this impairment contributes to persistence of the infection. In this study, we compare the killing efficacy of CD8(+) T-cell responses in mice acutely and persistently infected with the lymphocytic choriomeningitis virus, using an in vivo CTL killing assay. To infer the killing efficacy of CTLs, we developed a new mathematical model describing the disappearance of peptide-pulsed cells from the blood of the mice over time. We estimate a lower half-life for peptide-pulsed cells in acute infection than in persistent infection, which indicates a higher killing efficacy of the CD8(+) T-cell response in acute infection. However, by controlling for the different levels of CTLs in acutely and persistently infected mice, we find that CTLs in persistent infection are only two times less efficacious than CTLs in acute infections. These results strongly suggest that the in vivo cytotoxicity of CD8(+) T-cell responses in persistent infection is modulated via the number of CTLs rather than their individual functionality.