Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression
Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression
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DOI：
10.1182/blood.v99.6.2084
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发表时间：
2002-03-15
期刊：
影响因子：
20.3
通讯作者：
Kämpgen, E
中科院分区：
文献类型：
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作者：
McLellan, AD;Kapp, M;Kämpgen, E
小鼠脾脏含有 CD4(+)、CD8α(+) 和 CD4(-)/CD8α(-) 树突状细胞 (DC)，比例为 2:1:1。对 70 种表面和细胞质抗原的分析揭示了这 3 个亚群之间抗原表达的一些差异。值得注意的是，Birbeck 颗粒相关的 Langerin 抗原以及 CD103（大鼠 DC 标记 OX62 的小鼠同源物）由 CD8α(+) DC 亚群特异性表达。所有 DC 类型在 T 细胞区域以及脾边缘区都很明显，并且在胶原蛋白晶格中显示出相似的迁移能力。 3种DC亚型对同种异体CD4(+) T细胞的刺激作用相当。然而，即使在高刺激物与应答物比率下，CD8α(+) DC 对静息或激活的同种异体 CD8(+) T 细胞的刺激作用也非常弱，尽管使用 CD8(+) F5 T 细胞受体 (TCR) 转基因 T 细胞可以在最佳 DC/T 细胞比率和肽浓度下克服这一缺陷。 CD8α(-)或CD8α(+) DCs以相同的细胞毒性T淋巴细胞(CTL)裂解效率呈递同种抗原，并且它们的I类肽复合物周转率相似，因此CD8α DCs不能呈递抗原复合物或CD8α DCs抗原复合物的快速丢失并不是CD8α(+) DCs体外同种刺激能力低的原因。令人惊讶的是，CD8α（+）DC和CD4（-）/CD8（-）DC在静脉注射后均有效地引发了轻微的组织相容性（H-Y男性抗原）细胞毒性，而CD4（+）DC是CTL的弱诱导剂。因此，CD8α（+）DCs不能刺激CD8（+）T细胞仅限于某些体外测定，这些测定必须缺乏在体内CD8α（+）DCs和CD8（+）T细胞之间相互作用期间存在的某些增强信号。
Mouse spleen contains CD4(+), CD8alpha(+), and CD4(-)/CD8alpha(-) dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule-associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8alpha(+) DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC sub-types stimulated allogeneic CD4(+) T cells comparably. However, CD8alpha(+) DCs were very weak stimulators of resting or activated allogeneic CD8(+) T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8(+) F5 T-cell receptor (TCR)-transgenic T cells. CD8alpha(-) or CD8alpha(+) DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I-peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8alpha DCs was responsible for the low allostimulatory capacity of CD8alpha(+) DCs in vitro. Surprisingly, both CD8alpha(+) DCs and CD4(-)/CD8(-) DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4(+) DCs were weak inducers of CTLs. Thus, the inability of CD8alpha(+) DCs to stimulate CD8(+) T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo Interaction between CD8alpha(+) DCs and CD8(+) T cells.