Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis.
Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis.
复制标题
DOI：
10.1038/jid.2009.176
复制
发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
皮肤树突状细胞（DC）对皮肤免疫应答的精确贡献尚未得到很好的描述。我们开发了一种皮内（i.d.）注射模型，其中将表达卵清蛋白（OVA）肽特异性T细胞受体（Vα2/Vβ5）的CD 8 + T（OT-I）细胞直接递送至在表皮中表达OVA的转基因（Tg）小鼠的真皮。在ID之后注射后，这些小鼠在第7天可靠地发生皮肤GvHD。为了确定LC对随后的移植物抗宿主（GvHD）样反应的相对贡献，我们产生了K14-OVA × Langerin-Diphtheria-Toxin-Receptor（Langerin-DTR）Tg小鼠，以允许表皮中LC的条件性消融。为了描述真皮树突状细胞（dDC）在反应中的作用，我们还使用β-2-微球蛋白缺陷（b2 m）同源供体骨髓细胞产生了K14-OVA Tg嵌合体。这些小鼠中的真皮DC不能将OVA呈递给OT-I细胞，而LC具有抗原呈递能力。出乎意料的是，将OT-I细胞注射到白喉毒素（DT）处理的b2 m →K14-OVA × Langerin-DTR Tg小鼠中导致了皮肤GvHD。因此，在体内，LC和dDC似乎都能诱导角化细胞介导的CD 8介导的效应免疫应答。此外，令人惊讶的是，表达OVA的表皮细胞耗尽了不能启动同种异体表皮淋巴细胞反应的LC，在体外激活了幼稚的OT-I细胞。这些结果表明，角质形成细胞可能作为辅助细胞，有能力引发幼稚皮肤反应性T细胞。
The precise contribution(s) of skin dendritic cells (DCs) to immune responses in the skin has not been well delineated. We developed an intradermal (i.d.) injection model in which CD8+ T (OT-I) cells that express ovalbumin (OVA)-peptide-specific T-cell receptors (Vα2/Vβ5) are delivered directly to the dermis of transgenic (Tg) mice expressing OVA in the epidermis. Following i.d. injection, these mice reliably develop skin GvHD by day 7. To determine the relative contribution of LCs to the ensuing graft-versus-host (GvHD) - like reaction, we generated K14-OVA × Langerin-Diphtheria-Toxin-Receptor (Langerin-DTR) Tg mice to allow conditional ablation of LCs in the epidermis. To delineate the role of dermal dendritic cells (dDCs) in the reaction we also generated K14-OVA Tg chimeras using beta-2-microglobulin-deficient (b2m) congenic donor bone marrow cells. Dermal DCs in these mice cannot present OVA to OT-I cells while the LC are antigen presentation competent. Unexpectedly, OT-I cell injection into diphtheria toxin (DT)-treated b2m→K14−OVA × Langerin-DTR Tg mice resulted in skin GvHD. Thus, in vivo, both LC and dDC appear to be dispensable for induction of keratinocyte-directed, CD8-mediated effector immune responses. Furthermore and surprisingly, OVA-expressing epidermal cells depleted of LCs that could not initiate allogeneic epidermal lymphocyte reactions, activated naïve OT-I cells in vitro. These results indicate that keratinocytes may function as accessory cells-competent to prime naïve skin-reactive T cells.