Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties
Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties
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DOI：
10.1182/blood-2009-02-207795
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发表时间：
2009-09-24
期刊：
影响因子：
20.3
通讯作者：
Galipeau, Jacques
中科院分区：
文献类型：
--
作者：
Francois, Moira;Romieu-Mourez, Raphaelle;Galipeau, Jacques
最近涉及骨髓间充质干细胞（MSC）的研究表明，干扰素（IFN）-γ刺激诱导主要组织相容性复合物（MHC）II类介导的抗原呈递在MSC在体外和体内。一致地，我们研究了MSC通过其MHC I类分子呈递细胞外抗原的能力，这一过程称为交叉呈递。使用体外抗原呈递试验，我们证明了鼠MSC可以将可溶性卵清蛋白（OVA）交叉呈递给来自OT-I小鼠的幼稚CD 8（+）T细胞。MSC的交叉呈递依赖于蛋白酶体，部分依赖于与抗原加工分子相关的转运蛋白。用IFN-γ预处理MSC通过上调抗原加工和呈递增加交叉呈递。然而，尽管与抗原加工-1分子和免疫蛋白酶体亚基LMP 2相关的转运蛋白的转录由IFN-γ诱导被转化生长因子-β抑制，但在转化生长因子-β处理后，MSC的总体交叉呈递能力保持不变。这些观察结果通过在β 2-微球蛋白（-/-）小鼠中进行免疫重建试验进行了体内验证，并显示MSC的OVA交叉呈递诱导了初始OVA特异性CD 8（+）T细胞的增殖。总之，我们证明了MSC可以交叉呈递外源性抗原并诱导有效的CD 8（+）T细胞免疫应答，这一特性可以被开发为用于治疗癌症或感染性疾病的治疗性基于细胞的免疫生物药剂。（血。2009; 114：2632-2638）
Recent studies involving bone marrow mesenchymal stromal cells (MSCs) demonstrated that interferon (IFN)-gamma stimulation induces major histocompatibility complex (MHC) class II-mediated antigen presentation in MSCs both in vitro and in vivo. Concordantly, we investigated the ability of MSCs to present extracellular antigen through their MHC class I molecules, a process known as cross-presentation. Using an in vitro antigen presentation assay, we demonstrated that murine MSCs can cross-present soluble ovalbumin (OVA) to naive CD8(+) T cells from OT-I mice. Cross-presentation by MSC was proteasome dependent and partly dependent on transporter associated with antigen-processing molecules. Pretreatment of MSC with IFN-gamma increased cross-presentation by up-regulating antigen processing and presentation. However, although the transcription of the transporter associated with antigen processing-1 molecules and the immunoproteasome subunit LMP2 induced by IFN-gamma was inhibited by transforming growth factor-beta, the overall cross-presentation capacity of MSCs remained unchanged after transforming growth factor-beta treatment. These observations were validated in vivo by performing an immune reconstitution assay in beta(2)-microglobulin(-/-) mice and show that OVA cross-presentation by MSCs induces the proliferation of naive OVA-specific CD8(+) T cells. In conclusion, we demonstrate that MSCs can cross-present exogenous antigen and induce an effective CD8(+) T-cell immune response, a property that could be exploited as a therapeutic cell-based immune biopharmaceutic for the treatment of cancer or infectious diseases. (Blood. 2009; 114: 2632-2638)