CD8α+ plasmacytoid precursor DCs induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo
CD8α+ plasmacytoid precursor DCs induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo
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DOI：
10.1182/blood-2010-06-291187
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发表时间：
2011-02-24
期刊：
影响因子：
20.3
通讯作者：
Ildstad, Suzanne T.
中科院分区：
文献类型：
--
作者：
Huang, Yiming;Bozulic, Larry D.;Ildstad, Suzanne T.
CD 8阳性/T细胞受体阴性（CD 8（+）/TCR-）移植物促进细胞（FCs）是骨髓中的一种新型细胞群，其有效地增强造血干细胞（HSCs）的植入。以前，我们发现CD 11 c（+）/B220（+）/CD 11b（-）浆细胞样前体树突状细胞（p-preDC）FC亚群在易化过程中起着关键但非冗余的作用。在本研究中，我们研究了FC功能的机制。我们报道了FC在体内诱导抗原特异性CD 4（+）/CD 25（+）/FoxP 3（+）调节性T细胞（TCRs）。大多数嵌合T细胞是受体来源的。在移植后>= 4周收获的嵌合T细胞显著增强了供体和受者来源的HSC（但不是第三方HSC）在条件化的第二受体中的植入，证明了抗原特异性。尽管TGFAP在移植后2周和3周存在，但它们并没有增强植入。相比之下，第5周和更长时间的T细胞移植有效地增强了植入。嵌合体Tcl 3的功能与FoxP 3表达的发展直接相关。嵌合Tcl 4还在体外诱导对供体抗原的T细胞增殖的显著更强的抑制。去除p-preDC FC导致同种异体HSC的植入受损，并且不能产生嵌合TcB，这表明CD 8 α（+）p-preDC亚群在促进机制中是关键的。这些数据表明，FC在体内诱导抗原特异性T细胞的产生，其有效地增强同种异体HSC的植入。FC具有临床潜力，因为它们能够在体内保持致耐受性。（血。2011;117（8）：2494-2505）
CD8-positive/T-cell receptor-negative (CD8(+)/TCR-) graft facilitating cells (FCs) are a novel cell population in bone marrow that potently enhance engraftment of hemopoietic stem cells (HSCs). Previously, we showed that the CD11c(+)/B220(+)/CD11b(-) plasmacytoid-precursor dendritic cell (p-preDC) FC subpopulation plays a critical but nonredundant role in facilitation. In the present study, we investigated the mechanism of FC function. We report that FCs induce antigen-specific CD4(+)/CD25(+)/FoxP3(+) regulatory T cells (Tregs) in vivo. The majority of chimeric Tregs were recipient derived. Chimeric Tregs harvested at >= 4 weeks after transplantation significantly enhanced engraftment of donor-and recipient-derived HSCs, but not third-party HSCs, in conditioned secondary recipients, demonstrating antigen specificity. Although Tregs were present 2 and 3 weeks after transplantation, they did not enhance engraftment. In contrast, week 5 and greater Tregs potently enhanced engraftment. The function of chimeric Tregs was directly correlated with the development of FoxP3 expression. Chimeric Tregs also induced significantly stronger suppression of T-cell proliferation to donor antigen in vitro. Removal of p-preDC FCs resulted in impaired engraftment of allogeneic HSCs and failure to produce chimeric Tregs, suggesting that the CD8 alpha(+) p-preDC subpopulation is critical in the mechanism of facilitation. These data suggest that FCs induce the production of antigen-specific Tregs in vivo, which potently enhance engraftment of allogeneic HSCs. FCs hold clinical potential because of their ability to remain tolerogenic in vivo. (Blood. 2011;117(8):2494-2505)