Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells.
Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells.
复制标题
通过刺激未成熟的自体树突状细胞诱导自身反应性调节 T 细胞。
DOI：
10.1080/08820130601015775
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发表时间：
2007
影响因子：
2.8
通讯作者：
Miller,Joshua
中科院分区：
文献类型：
--
作者：
Jin,Yide;Fuller,Laphalle;Esquenazi,Violet;Blomberg,BonnieB;Burke3rd,GeorgeW;Ciancio,Gaetano;Tzakis,AndreasG;Ricordi,Camillo;Miller,Joshua
我们已经在供体骨髓输注的肾移植受者中的离体研究中显示，从受者的骨髓中提取的供体或受者来源的嵌合细胞下调受者的细胞免疫应答。在本研究中，我们现在已经通过用源自（免疫抑制的）肾移植受体的骨髓细胞（BMC）或实验室志愿者的PBMC（即，分别为ibDC和ipDC）。这些由ibDC和ipDC诱导的调节性T细胞具有自身反应性，并被命名为具有相似表型和功能特征的TA和TAP。它们主要是CD 4 + CD 25高、CD 45 RA低和CD 45 RO高，并且均匀表达细胞内CTLA-4以及IL-4、IL-10、Foxp 3的信息，并差异表达TGFβ。它们对自体成熟树突状刺激细胞（mDC）的增殖反应是对同种异体mDC的两倍强，对同种异体mDC的增殖反应显著低于（对照）自体TPBL的增殖反应，表明无反应性状态。TA和TAP对表达EB病毒（EBV）抗原的自体细胞没有细胞毒性，但能够抑制（调节）这种TPBL对自体和同种异体EBV淋巴母细胞的反应的效应期。这种调节似乎需要细胞与细胞的接触。
We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAband TApwith similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL-4, IL-10, Foxp3, and differentially expressed TGFβ. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were ∼two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAband TApwere not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBLresponse to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact.