Department of Renal Transplant, Center of Nephropathy, The First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, 710061 Shaanxi, China.
Transpl Immunol. 2012 Jan;26(1):19-26. doi: 10.1016/j.trim.2011.10.001. Epub 2011 Oct 8.
Immunoglobulin-like transcript 3 (ILT3) belongs to a family of inhibitory receptors with cytoplasmic immunoreceptor tyrosine based inhibitory motifs (ITIMs). Numerous studies have reported that increased ILT3 expression is associated with the tolerogenic properties of antigen-presenting cells (APCs) including dendritic cells (DCs). In this study, human CD34(+) hematopoietic stem/progenitor cells (HPSCs) were transduced with self-inactivating lentiviral vector carrying the ILT3 gene, and then induced to differentiate into DCs. Long-term and sustained transgene expression were observed. Importantly, DCs differentiated from ILT3-transduced HPSCs expressed high levels of human ILT3 and acquired strong tolerogenic capacity. This effect was associated with markedly decreased expression of co-stimulatory molecules (CD80, CD86) and down-regulation of NF-κB. Functionally, ILT3(high) DCs showed a reduced capacity to stimulate allogeneic T cell proliferation and increased the production of CD4(+)CD25(+)Foxp3(+) T regulatory cells with immunosuppressive activity. These results demonstrate that DCs derived from ILT3-transduced human CD34(+)HPSCs display tolerogenic properties to induce T regulatory cells in vitro.
免疫球蛋白样转录因子 3（ILT3）属于抑制性受体家族，具有细胞质免疫受体酪氨酸抑制基序（ITIM）。许多研究表明，ILT3 表达增加与抗原呈递细胞（APCs）的耐受特性有关，包括树突状细胞（DCs）。在这项研究中，人 CD34(+)造血干细胞/祖细胞（HPSCs）被携带 ILT3 基因的自我失活慢病毒载体转导，然后诱导分化为 DCs。观察到长期和持续的转基因表达。重要的是，从 ILT3 转导的 HPSCs 分化而来的 DCs 表达高水平的人 ILT3 并获得了强大的耐受能力。这种效应与共刺激分子（CD80、CD86）的表达显著降低和 NF-κB 的下调有关。功能上，ILT3(高)DCs 刺激同种异体 T 细胞增殖的能力降低，增加了具有免疫抑制活性的 CD4(+)CD25(+)Foxp3(+)T 调节细胞的产生。这些结果表明，从 ILT3 转导的人 CD34(+)HPSCs 中分化而来的 DCs 具有体外诱导 T 调节细胞的耐受特性。
