CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo.

CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo.
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DOI:
10.1084/jem.192.12.1685
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发表时间:
2000-12-18
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Bevan MJ
Bevan MJ
中科院分区:
其他
文献类型:
--
作者:
den Haan JM;Lehar SM;Bevan MJ

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骨髓来源的抗原呈递细胞(APC)摄取细胞相关抗原,并在称为交叉致敏的过程中将其在主要组织相容性复合体(MHC)I类分子的背景下呈递给CD 8 + T细胞。交叉致敏对于诱导针对在专职APC中不表达的抗原的CD 8 + T细胞应答是必不可少的。尽管体外实验已经表明树突状细胞(DC)和巨噬细胞能够呈递与MHC I类相关的外源性抗原,但体内交叉呈递细胞尚未被鉴定。我们在体内用卵清蛋白负载的β2-微球蛋白缺陷的脾细胞引发后分离了脾DC,并表明它们确实在MHC I类分子的背景下呈递细胞相关抗原。这一过程是抗原呈递相关转运蛋白(TAP)依赖性的,表明内体到胞质溶胶的转运。为了确定脾脏DC的特定亚群是否参与这种交叉呈递,我们阴性和阳性选择了CD 8 −和CD 8 + DC。只有CD 8+,而不是CD 8-,DC亚群表现出交叉致敏能力。在注射装载有荧光珠的脾细胞后的FACS®研究显示,分别有1%和0.6%的CD 8+和CD 8 − DC亚群具有一个或多个相关珠。这些结果表明,CD 8 + DC在产生细胞相关抗原特异性细胞毒性T淋巴细胞应答中起重要作用。
Bone marrow–derived antigen-presenting cells (APCs) take up cell-associated antigens and present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells in a process referred to as cross-priming. Cross-priming is essential for the induction of CD8+ T cell responses directed towards antigens not expressed in professional APCs. Although in vitro experiments have shown that dendritic cells (DCs) and macrophages are capable of presenting exogenous antigens in association with MHC class I, the cross-presenting cell in vivo has not been identified. We have isolated splenic DCs after in vivo priming with ovalbumin-loaded β2-microglobulin–deficient splenocytes and show that they indeed present cell-associated antigens in the context of MHC class I molecules. This process is transporter associated with antigen presentation (TAP) dependent, suggesting an endosome to cytosol transport. To determine whether a specific subset of splenic DCs is involved in this cross-presentation, we negatively and positively selected for CD8− and CD8+ DCs. Only the CD8+, and not the CD8−, DC subset demonstrates cross-priming ability. FACS® studies after injection of splenocytes loaded with fluorescent beads showed that 1 and 0.6% of the CD8+ and the CD8− DC subsets, respectively, had one or more associated beads. These results indicate that CD8+ DCs play an important role in the generation of cytotoxic T lymphocyte responses specific for cell-associated antigens.
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