Requirement for interactions of natural killer T cells and myeloid-derived suppressor cells for transplantation tolerance.
Requirement for interactions of natural killer T cells and myeloid-derived suppressor cells for transplantation tolerance.
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DOI：
10.1111/ajt.12914
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Strober S
中科院分区：
文献类型：
--
作者：
Hongo D;Tang X;Baker J;Engleman EG;Strober S
该研究的目的是阐明细胞和分子机制，通过该机制，小鼠骨髓和心脏联合移植的临床适用免疫耐受方案导致混合嵌合体和移植物接受。淋巴照射和抗T细胞抗体的预处理方案改变了淋巴组织中细胞的平衡，以产生耐受原性微环境，从而有利于自然杀伤T（NKT）细胞、CD 4 + CD 25 + TcR和Gr-1+ CD 11b+髓源性抑制细胞（MDSC）的增加，超过常规T细胞。MDSC的耗竭消除了嵌合和耐受，并且这些纯化的细胞的添加是恢复性的。预处理方案激活了MDSC，通过增加的CD 34 -1、IL-4 R α和PDL 1的表达来判断，并且激活的细胞获得了在混合白细胞反应中抑制常规T细胞向同种异体抗原增殖的能力。MDSC的激活依赖于宿主不变NKT细胞的存在。预处理方案使宿主不变的NKT细胞向IL-4分泌极化，并且MDSC活化依赖于IL-4。总之，嵌合和耐受需要MDSC，并且它们的抑制功能依赖于它们与NKT细胞和IL-4的相互作用。
The goal of the study was to elucidate the cellular and molecular mechanisms by which a clinically applicable immune tolerance regimen of combined bone marrow and heart transplants in mice results in mixed chimerism and graft acceptance. The conditioning regimen of lymphoid irradiation and anti-T cell antibodies changed the balance of cells in the lymphoid tissues to create a tolerogenic microenvironment favoring the increase of natural killer T (NKT) cells, CD4+CD25+ Tregs, and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs), over conventional T cells. The depletion of MDSCs abrogated chimerism and tolerance, and add back of these purified cells was restorative. The conditioning regimen activated the MDSCs as judged by the increased expression of arginase-1, IL-4Rα, and PDL1, and the activated cells gained the capacity to suppress the proliferation of conventional T cells to alloantigens in the mixed leukocyte reaction. MDSC activation was dependent on the presence of host invariant NKT cells. The conditioning regimen polarized the host invariant NKT cells toward IL-4 secretion, and MDSC activation was dependent on IL-4. In conclusion, there was a requirement for MDSCs for chimerism and tolerance, and their suppressive function was dependent on their interactions with NKT cells and IL-4.
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影响因子：
17.1
作者：
Leventhal J;Abecassis M;Miller J;Gallon L;Ravindra K;Tollerud DJ;King B;Elliott MJ;Herzig G;Herzig R;Ildstad ST
通讯作者：
Ildstad ST
影响因子：
11.5
作者：
Konishi, J;Yamazaki, K;Nishimura, M
通讯作者：
Nishimura, M
影响因子：
50.3
作者：
Ahn, G-One;Brown, J. Martin
通讯作者：
Brown, J. Martin
影响因子：
20.3
作者：
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.
影响因子：
4.4
作者：
Higuchi, M;Zeng, DF;Strober, S
通讯作者：
Strober, S