Adaptive immunity and enhanced CD8+ T cell response to Listeria monocytogenes in the absence of perforin and IFN-γ
Adaptive immunity and enhanced CD8+ T cell response to Listeria monocytogenes in the absence of perforin and IFN-γ
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DOI：
10.4049/jimmunol.164.12.6444
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发表时间：
2000-06-15
影响因子：
4.4
通讯作者：
Harty, JT
中科院分区：
文献类型：
--
作者：
Badovinac, VP;Harty, JT
来自IFN-γ缺陷（GKO）或穿孔素缺陷（PKO）小鼠的单个Ag特异性CD 8（+）T细胞提供针对单核细胞增多性李斯特菌的鼠感染的实质性免疫。为了解决穿孔素和IFN-γ之间冗余作为CD 8（+）T细胞效应机制的可能性，我们产生穿孔素/IFN-γ（PKO/GKO）双缺陷小鼠。对免疫显性溶血素O（LL 0 91 -99）表位特异的PKO/GKO衍生的CD 8 + T细胞提供对LM感染的免疫力，其类似于肝脏中Ag匹配的野生型（WT）CD 8（+）T细胞提供的免疫力，但在脾脏中降低。引人注目的是，来自免疫的PKO/GKO小鼠的多克隆CD 8（+）T细胞在减少细菌数量方面比来自免疫的WT小鼠的相同数量的多克隆CD 8（+）T细胞强100倍。该结果可能是定量的，因为在相同免疫后7天，PKO/GKO小鼠中针对免疫显性LLO 91 -99表位的CD 8（+）T细胞应答的频率比WT小鼠高>4.5倍。此外，PKO/GKO小鼠可以通过用减毒李斯特菌单次感染来免疫，以抵抗比幼稚PKO/GKO小鼠高> 80，000倍的毒性生物体的攻击。这些数据表明，无论是穿孔素或IFN-γ是需要的发展或表达的适应性免疫LM，此外，结果表明，穿孔素和IFN-γ的潜力，以调节的幅度的CD 8（+）T细胞对感染的反应。
Single Ag-specific CD8(+) T cells from IFN-gamma-deficient (GKO) or perforin-deficient (PKO) mice provide substantial immunity against murine infection with Listeria monocytogenes, To address the potential for redundancy between perforin and IFN-gamma as CD8(+) T cell effector mechanisms, we generated perforin/IFN gamma (PKO/GKO) double deficient mice. PKO/GKO-derived CDS' T cells specific for the immunodominant listeriolysin O (LLO91-99) epitope provide immunity to LM infection similar to that provided by Ag-matched wild-type (WT) CD8(+) T cells in the liver but reduced in the spleen. Strikingly, polyclonal CD8(+) T cells from immunized PKO/GKO mice were similar to 100-fold more potent in reducing bacterial numbers than the same number of polyclonal CD8(+) T cells from immunized WT mice. This result is probably quantitative, because the frequency of the CD8(+) T cell response against the immunodominant LLO91-99 epitope is >4.5-fold higher in PKO/GKO mice than WT mice at 7 days after identical immunizations. Moreover, PKO/GKO mice can be immunized by a single infection with attenuated Listeria to resist >80,000-fold higher challenges with virulent organisms than naive PKO/GKO mice. These data demonstrate that neither perforin nor IFN-gamma is required for the development or expression of adaptive immunity to LM, In addition, the results suggest the potential for perforin and IFN-gamma to regulate the magnitude of the CD8(+) T cell response to infection.