A recombinant Sendai virus is controlled by CD4+ effector T cells responding to a secreted human immunodeficiency virus type 1 envelope glycoprotein
A recombinant Sendai virus is controlled by CD4+ effector T cells responding to a secreted human immunodeficiency virus type 1 envelope glycoprotein
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DOI：
10.1128/jvi.00197-07
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发表时间：
2007-11-01
影响因子：
5.4
通讯作者：
Slobod, Karen S.
中科院分区：
文献类型：
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作者：
Brown, Scott A.;Hurwitz, Julia L.;Slobod, Karen S.
抗原特异性CD 4（+）辅助性T细胞在病毒感染中的重要性已得到公认，但其作为病毒清除直接介质的可能作用尚不清楚。在这里，我们描述了一种重组仙台病毒的策略，用于探测CD 4（+）T细胞的效应作用。用编码分泌型人类免疫缺陷病毒1型（HIV-1）包膜蛋白的DNA和牛痘病毒重组载体接种小鼠，然后用携带同源HIV-1包膜基因的仙台病毒攻击。致敏小鼠表现出（i）大量经病毒致敏的CD 4（+）T细胞群迅速归巢至病毒感染的肺，（ii）在该部位大量产生γ干扰素和白细胞介素-2（IL-2）、IL-4和IL-5，以及（iii）显著降低肺病毒载量。在存在或不存在CD 8（+）和/或CD 4（+）T细胞的情况下，用免疫球蛋白（-/-）mu MT小鼠重复激发实验。这些选择性免疫缺陷小鼠在缺乏抗体或CD 8（_）（+）T细胞的情况下受到致敏的CD 4（+）T细胞的保护。总之，这些结果突出了CD 4（+）T细胞作为体内直接效应子的作用，并且由于该方案给出了如此有效的应答，因此确定了用于进一步剖析肺中CD 4 + T细胞介导的免疫的杰出实验模型。
The importance of antigen-specific CD4(+) helper T cells in virus infections is well recognized, but their possible role as direct mediators of virus clearance is less well characterized. Here we describe a recombinant Sendai virus strategy for probing the effector role(s) of CD4(+) T cells. Mice were vaccinated with DNA and vaccinia virus recombinant vectors encoding a secreted human immunodeficiency virus type 1 (HIV-1) envelope protein and then challenged with a Sendai virus carrying a homologous HIV-1 envelope gene. The primed mice showed (i) prompt homing of numerous envelope-primed CD4(+) T cell populations to the virus-infected lung, (ii) substantial production of gamma interferon, and interleukin-2 (IL-2), IL-4, and IL-5 in that site, and (iii) significantly reduced pulmonary viral load. The challenge experiments were repeated with immunoglobulin(-/-) mu MT mice in the presence or absence of CD8(+) and/or CD4(+) T cells. These selectively immunodeficient mice were protected by primed CD4(+) T cells in the absence of antibody or CD8(_)(+) T cells. Together, these results highlight the role of CD4(+) T cells as direct effectors in vivo and, because this protocol gives such a potent response, identify an outstanding experimental model for further dissecting CD4+ T-cell-mediated immunity in the lung.