Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts.
Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts.
复制标题
DOI：
10.1097/tp.0b013e318186fccd
复制
发表时间：
2008-10-27
期刊：
影响因子：
6.2
通讯作者：
Horuzsko A
中科院分区：
文献类型：
--
作者：
Zhang W;Liang S;Wu J;Horuzsko A
在同种异体识别过程中HLA-G的表达与更好的移植物接受性相关。抑制性受体ILT 2在活化的T细胞上表达，并用于关闭T细胞活化，最终导致T细胞死亡或诱导无反应性。HLA-G-ILT 2相互作用的免疫抑制完成的潜在机制之一涉及骨髓源性抑制细胞（MDSC）的扩增。MDSC在移植中的潜力尚未被开发。(1)在小鼠中获得了通过抑制性受体ILT 2及其配体扩增的MDSC的详细表型特征、免疫抑制潜力以及同种异体移植激活的MDSC。(2)进行寡核苷酸和实时途径特异性PCR阵列以表征ILT 2特异性MDSC。(3)研究了过继转移MDSC后的皮肤移植物存活。ILT 2受体的结合，特别是HLA-G的结合，扩大了MDSC的群体，具有增强的抑制活性。通过ILT 2受体及其配体产生的MDSC的连续转移延长了同种异体皮肤移植受者的移植物存活。我们已经提出了通过ILT 2和HLA-G增强免疫抑制活性和扩增MDSC的途径。我们的研究结果表明，使用ILT 2抑制性受体/HLA-G配体诱导MDSC可能是一种有吸引力的策略，用于预防临床移植中高免疫原性器官/组织的排斥反应。
The expression of HLA-G during allogeneic recognition is associated with better graft acceptance. The inhibitory receptor ILT2 is expressed on activated T cells and serves to shut down T cell activation, culminating in T cell death or induction of anergy. One of the potential mechanisms in the immunosuppressive accomplishment of HLA-G-ILT2 interactions involves the expansion of myeloid-derived suppressor cells (MDSCs). The potential of MDSCs in transplantation has not yet been exploited. (1) Detailed phenotypic characteristics, immunosuppressive potential of MDSCs expanded via inhibitory receptor ILT2 and its ligands, and allogeneic transplant-activated MDSCs were obtained in mice. (2) Oligo- and Real-time pathway-specific PCR Arrays were performed to characterize ILT2-specific MDSCs. (3) Skin allograft survival after adoptive transfer of MDSCs was studied. Engagement of ILT2 receptors, especially by HLA-G, expanded the population of MDSCs with enhanced suppressive activity. Adoptive transfer of MDSCs generated via ILT2 receptor and its ligands prolonged graft survival in recipients of allogeneic skin transplant. We have proposed pathways for enhancement of immunosuppressive activities and expansion of MDSCs via ILT2 and HLA-G. Our results suggest that induction of MDSCs using ILT2 inhibitory receptor/HLA-G ligand may be an attractive strategy for preventing rejection of highly immunogenic organs/tissues in clinical transplantation.