Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.

Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.
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DOI:
10.1084/jem.20032083
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发表时间:
2004-06-07
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Autran B
Autran B
中科院分区:
其他
文献类型:
--
作者:
Combadiere B;Boissonnas A;Carcelain G;Lefranc E;Samri A;Bricaire F;Debre P;Autran B

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自1980年疫苗接种结束以来,对天花病毒的残留免疫提出了关于在没有抗原的情况下长期免疫记忆持续存在的关键问题。在末次免疫后13-25年的79名接种者和未接种者中比较了产生IFN-γ的效应记忆和增殖记忆T细胞。只有20%的疫苗接种者在第6天同时显示出产生IFN-γ的即时效应记忆应答和增殖记忆应答; 52.5%仅显示增殖应答; 27.5%完全没有可检测到的疫苗特异性应答。这两种反应均由CD 4和CD 8 T细胞介导。疫苗特异性IFN-γ产生细胞主要由CD 4Pos、CD 45 RANeg、CD 11 aHi、CD 27 Pos和CCR 7 Neg T细胞组成。它们的频率较低,但可在体外扩增7 d内。首次免疫后的时间影响了它们的持久性:它们在引发后45年消失,但增殖反应仍然可以检测到。回忆的次数并不影响残留效应记忆T细胞的持久性。程序性再接种可在回忆后2个月内增强IFN-γ和增殖反应,即使在先前无法检测到残留效应记忆细胞的疫苗接种者中也是如此。在没有天花病毒的情况下,这种牛痘特异性免疫记忆的长期维持改变了我们对痘病毒长期记忆持久性机制的理解,并挑战了疫苗接种策略。
Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-γ–producing effector–memory and proliferative memory T cells were compared in 79 vaccinees 13–25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-γ–producing effector–memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-γ–producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector–memory T cells. Programmed revaccination boosted both IFN-γ and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector–memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.
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影响因子: --
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