Generation of antigen-specific CD8+ CTLs from naive precursors.
Generation of antigen-specific CD8+ CTLs from naive precursors.
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DOI：
10.4049/jimmunol.153.3.996
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发表时间：
1994-08
影响因子：
4.4
通讯作者：
A. Mehta-Damani;S. Markowicz;E. Engleman
中科院分区：
文献类型：
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作者：
A. Mehta-Damani;S. Markowicz;E. Engleman
I类MHC限制性CTL是针对病毒感染的宿主免疫应答的重要组成部分，并且CTL效应物通常可以从感染的个体分离。然而，人们对诱导CTL的机制还不完全了解，部分原因是在体外从幼稚前体产生此类细胞很困难。在本研究中，我们使用了人外周血树突状细胞（DC），缺乏的CD 4 + T细胞，致敏幼稚的CD 8 + T细胞的外源性抗原，导致在Ag特异性CTL效应器的产生。利用该系统，产生了针对复杂糖蛋白、匙孔血蓝蛋白和来自HIV-1 gag和包膜蛋白的保守区域的多个小（9-15个氨基酸）合成肽的Ag特异性CTL系。HIV-1特异性CTL表现出有效的HLA I类限制性杀伤Ag脉冲和病毒感染的靶细胞。与Ag脉冲的DC相反，Ag脉冲的单核细胞未能使CTL前体敏化，尽管它们可以用作用于CTL扩增目的的饲养细胞和在细胞溶解测定中用作靶细胞。通过使用本文所述的系统，对外源Ag的原代人T细胞应答的详细分析现在是可行的，并且可以产生具有所需特异性的CTL用于过继免疫治疗方案中的潜在临床用途。
Class I MHC-restricted CTLs are an important component of the host immune response against viral infections, and CTL effectors can often be isolated from infected individuals. However, the mechanism responsible for the induction of CTLs is incompletely understood because, in part, of the difficulty in generating such cells in vitro from naive precursors. In the present study we have used human peripheral blood dendritic cells (DCs), devoid of CD4+ T cells, to sensitize naive CD8+ T cells to exogenous Ags, resulting in the generation of Ag specific CTL effectors. With this system, Ag-specific CTL lines were generated to a complex glycoprotein, keyhole limpet hemocyanin, and to multiple small (9-15 amino acids) synthetic peptides derived from conserved regions of the HIV-1 gag and envelope proteins. The HIV-1-specific CTLs demonstrated potent HLA class I restricted killing of both Ag pulsed and virally infected target cells. In contrast to Ag-pulsed DCs, Ag-pulsed monocytes failed to sensitize CTL precursors although they could be used as feeders for purposes of CTL expansion and as target cells in cytolytic assays. With the use of the system described herein, a detailed analysis of the primary human T cell response to foreign Ags is now feasible, and CTL of desired specificity can be generated for potential clinical use in adoptive immunotherapy protocols.