CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients
CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients
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DOI：
10.1183/09031936.00093207
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发表时间：
2008-06-01
影响因子：
24.3
通讯作者：
Magnan, A.
中科院分区：
文献类型：
--
作者：
Botturi, K.;Lacoeuille, Y.;Magnan, A.
闭塞性细支气管炎（OB）是长期肺移植物丢失的主要原因，这是由于在供体免疫细胞缺乏的情况下发生的免疫过程不清楚。作者假设OB患者自体树突状细胞（DCs）与T细胞的相互作用可能与健康肺移植受者（LTR）不同。将14例OB和35例非OB LTR的单核细胞来源的DCs与自体T细胞一起培养。通过流式细胞术评估T调节性（Treg）细胞、共受体、细胞因子产生、DC表型和吲哚胺2，3-双加氧酶（IDO）表达。在铜绿假单胞菌或抗共受体抗体存在下重复实验，来自非OB LTR的DC上调Treg细胞、细胞毒性T淋巴细胞抗原（CTLA）-4和白细胞介素（IL）-10。相比之下，CD 28和诱导型T细胞共刺激分子与IL-13和IL-4同时下调。与OB相比，非OB DC显示出具有较低的CD 80和CD 83以及较高的IDO表达水平的不成熟表型。铜绿假单胞菌的刺激不能消除DC对非OB T细胞的致耐受性作用。最后，减少Treg细胞和IL-10的生产被检测到时，加入抗CTLA-4抗体在非OB LTR。本研究表明，树突状细胞从非闭塞性细支气管炎肺移植受体诱导耐受T细胞表型，这是依赖于细胞毒性T淋巴细胞抗原-4订婚。
Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of the donor's immune cells. The present authors hypothesised that interactions of autologous dendritic cells (DCs) with T-cells could differ in OB patients compared with healthy lung transplant recipients (LTRs).Monocyte-derived DCs from 14 OB and 35 non-OB LTRs were cultured with autologous T-cells. T-regulatory (Treg) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3-dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in the presence of Pseudomonas aeruginosa or anti-co-receptor antibodies.DCs from non-OB LTR upregulated Treg cells, cytotoxic T-lymphocyte antigen (CTLA)-4 and interleukin (IL)-10. By contrast CD28 and inducible T-cell co-stimulator were downregulated concomitantly to IL-13 and IL-4. Compared to OB, non-OB DCs displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation by P. aeruginosa did not abolish the tolerogenic effects of DCs on non-OB T-cells. Finally, decreased Treg cells and IL-10 production were detected when adding anti-CTLA-4 antibodies in non-OB LTR.The present study demonstrates that dendritic cells from nonobliterative bronchiolitis lung transplant recipients induce a tolerant T-cell phenotype which is dependent on cytotoxic T-lymphocyte antigen-4 engagement.