Ly6C(low) monocytes differentiate into dendritic cells and cross-tolerize T cells through PDL-1.
Ly6C(low) monocytes differentiate into dendritic cells and cross-tolerize T cells through PDL-1.
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DOI：
10.4049/jimmunol.0803172
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
--
作者：
Peng Y;Latchman Y;Elkon KB
单核细胞来源的树突状细胞是抗感染免疫反应的积极参与者，但它们在稳态条件下是否在维持自身耐受方面发挥作用尚不清楚。在这里，我们研究了单核细胞的分化，它们摄取凋亡细胞的能力，以及它们在体内的潜在功能。我们观察到，Ly6C(Gr-1)低成熟单核细胞上调其在脾中的MHC II水平，表达高水平的PDL-1(程序性死亡配体1)，并且在体内摄取凋亡细胞方面比Ly6Chigh未成熟单核细胞更有效。分选的循环Ly6Clow单核细胞能够交叉呈现细胞凋亡相关的OVA和可溶性OVA蛋白。含有凋亡细胞的单核细胞可进一步分化为CD11c+CD8MHC II+脾树突状细胞，维持α−-1的高表达。由于含有凋亡细胞相关OVA的野生型而非PDL-1缺陷的外周血单核细胞抑制了对OVA免疫的反应，因此单核细胞介导的T细胞耐受需要PDL-1的表达。这些观察表明，Ly6Clow成熟单核细胞可以通过依赖PDL-1的机制促进对凋亡细胞中自身抗原的耐受。
Monocyte-derived dendritic cells are active participants during the immune response against infection, but whether they play a role in maintaining self-tolerance under steady-state conditions is not known. Here we investigated the differentiation of monocytes, their ability to ingest apoptotic cells, and their potential functionality in vivo. We observed that Ly6C (Gr-1)low mature monocytes up-regulate their MHC II level in the spleen, express high levels of PDL-1 (programmed death ligand 1), and are more efficient than Ly6Chigh immature monocytes in the ingestion of apoptotic cells in vivo. Sorted circulating Ly6Clow monocytes were able to cross-present both apoptotic cell-associated OVA and soluble OVA protein. Monocytes containing apoptotic cells can further differentiate into CD11c+CD8α− MHC II+ splenic dendritic cells that maintained high expression of PDL-1. Since wild-type but not PDL-1-deficient peripheral blood monocytes containing apoptotic cell-associated OVA suppressed the response to OVA immunization, PDL-1 expression was required for monocyte-mediated T cell tolerance. These observations demonstrate that Ly6Clow mature monocytes can promote tolerance to self Ag contained in apoptotic cells through a PDL-1-dependent mechanism.
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DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
20.3
作者：
McCloskey, TW;Bakshi, S;Pahwa, S
通讯作者：
Pahwa, S
影响因子：
16.8
作者：
Carbone, FR;Belz, GT;Heath, WR
通讯作者：
Heath, WR
影响因子：
56.9
作者：
Fogg, DK;Sibon, C;Geissmann, F
通讯作者：
Geissmann, F