The role of B7-1 and B7-2 costimulation for the generation of CTL responses in vivo.
The role of B7-1 and B7-2 costimulation for the generation of CTL responses in vivo.
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DOI：
10.4049/jimmunol.161.6.2740
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
Luis J. Sigal;Hans Reiser;Kenneth L. Rock
中科院分区：
文献类型：
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作者：
Luis J. Sigal;Hans Reiser;Kenneth L. Rock
B7-1和B7-2共刺激分子在Ag特异性CD 8 + CTL产生中的作用还不清楚。在本文中，我们分析了B7-1和B7-2在针对非活体、外源性抗原和活病毒产生CTL中的作用。为了分析B7共刺激在CTL诱导中的作用，我们通过注射抗B7 - 1和/或抗B7 - 2单克隆抗体在体内阻断B7 - 1和/或B7 -2;随后用已经与作为外源性Ag模型的珠交联的鸡OVA或用野生型型和表达不同形式鸡卵清蛋白的重组牛痘病毒作为病毒Ags的模型。我们的研究结果表明，B7共刺激是必要的，在所有这些抗原的CTL的产生。由于B7分子可以共刺激野生型动物中的CD 8+和/或CD 4 + T细胞，我们还研究了共刺激在缺乏大多数CD 4 + T细胞的MHC II类缺陷小鼠中产生针对外源性和病毒性Ag的CTL中的作用。在这些动物中，两种mAb的组合也阻断了所有CTL应答，表明CTL的Th细胞非依赖性活化依赖于提供给CD 8+细胞的B7共刺激信号。这些发现有助于理解共刺激对CTL产生的作用。我们还讨论了这些研究结果的影响，在启动CTL反应的专业APC的作用。
The role of B7-1 and B7-2 costimulatory molecules in the generation of Ag-specific CD8+ CTLs is not well understood. In this paper, we analyze the role of both B7-1 and B7-2 in the generation of CTLs to nonliving, exogenous Ag and to live virus. To analyze the role of B7 costimulation in the induction of CTLs, we blocked B7-1 and/or B7-2 in vivo by injecting C57BL/6 mice with anti-B7-1 and/or anti-B7-2 mAbs; the mice were subsequently immunized with either chicken OVA that had been cross-linked to beads as a model of exogenous Ags or with wild-type and recombinant vaccinia virus expressing different forms of chicken OVA as models of viral Ags. Our results indicate that B7 costimulation is necessary in the generation of CTLs for all of these Ags. Since the B7 molecules could be costimulating CD8+ and/or CD4+ T cells in wild-type animals, we also examined the role of costimulation in the generation of CTLs to exogenous and viral Ag in MHC class II-deficient mice lacking most CD4+ T cells. In these animals, a combination of both mAbs also blocked all CTL responses, indicating that the Th cell-independent activation of CTLs is dependent upon the B7-costimulatory signals supplied to the CD8+ cell. These findings contribute to the understanding of the role of costimulation for the generation of CTLs. We also discuss the implications of these findings on the role of professional APCs in the initiation of CTL responses.