Furuzawa-Carballeda Janette, Lima Guadalupe, Simancas Perla, Ramos-Bello Dolores, Simancas Margaret, Bostock Ian C, Vilatobá Mario, Gabilondo Bernardo, Granados Julio, Morales-Buenrostro Luis, Alberú Josefina, Llorente Luis
Department of Immunology and Rheumatology, National Institute of Medical Sciences and Nutrition, 14000 Mexico City, DF, Mexico.
J Transplant. 2012;2012:256960. doi: 10.1155/2012/256960. Epub 2012 Nov 19.
Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. These subpopulations also might participate in maintaining allograft immunological quiescence in kidney transplant recipients (KTRs) with an excellent long-term graft function under immunosuppression (ELTGF). The aim of the study was to characterize and to enumerate peripheral Tregs, Bregs, and DCregs in KTR with an ELTGF for more than 5 years after transplant. Fourteen KTR with an ELTGF, 9 KTR with chronic graft dysfunction (CGD), and 12 healthy donors (HDs) were included in the study. CD19(+)-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4(+)/CD25(hi), and CD8(+)/CD28(-) Tregs, as well as CCR6(+)/CD123(+)/IDO(+) DCs, were quantitated by flow cytometry. IL-10-producing Bregs (immature/transitional, but not CD19(+)/CD38(hi)/CD24(hi)/CD27(+)B10 cells), CCR6(+)/CD123(+)/IDO(+) DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (P < 0.05). By contrast, number of Tregs, DCregs, and Bregs except for CD27(+)B10 cells from CGD patients had lower levels versus HD and ELTGF patients (P < 0.05). The findings of this exploratory study might suggest that in ELTGF patients, peripheral tolerance mechanisms could be directly involved in the maintenance of a quiescent immunologic state and graft function stability.
表达调节性Foxp3的T细胞（Tregs）、产生IL-10的B细胞（Bregs）和表达吲哚胺2,3-双加氧酶（IDO）的树突状细胞（DCregs）可下调炎症过程并诱导外周耐受。这些亚群也可能参与维持肾移植受者（KTRs）的同种异体移植免疫静止状态，这些受者在免疫抑制下具有出色的长期移植功能（ELTGF）。本研究的目的是对移植后5年以上具有ELTGF的KTR中的外周Tregs、Bregs和DCregs进行特征描述和计数。本研究纳入了14例具有ELTGF的KTR、9例具有慢性移植功能障碍（CGD）的KTR和12例健康供者（HDs）。通过阳性选择纯化表达CD19(+)的外周B淋巴细胞。通过流式细胞术对产生IL-10的B细胞、CD4(+)/CD25(hi)和CD8(+)/CD28(-) Tregs以及CCR6(+)/CD123(+)/IDO(+) DCs进行定量分析。来自ELTGF患者的产生IL-10的Bregs（未成熟/过渡型，但不是CD19(+)/CD38(hi)/CD24(hi)/CD27(+) B10细胞）、CCR6(+)/CD123(+)/IDO(+) DCs和Tregs与HD相比具有相似或更高的百分比（P < 0.05）。相比之下，来自CGD患者的Tregs、DCregs和除CD27(+) B10细胞外的Bregs数量与HD和ELTGF患者相比更低（P < 0.05）。这项探索性研究的结果可能表明，在ELTGF患者中，外周耐受机制可能直接参与维持静止的免疫状态和移植功能稳定性。
