Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN-γ+ blood lymphocytes in kidney transplant recipients with good long-term graft outcome
Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN-γ+ blood lymphocytes in kidney transplant recipients with good long-term graft outcome
复制标题
DOI：
10.1111/j.1432-2277.2008.00662.x
复制
发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Opelz, Gerhard
中科院分区：
文献类型：
--
作者：
Daniel, Volker;Naujokat, Cord;Opelz, Gerhard
有证据表明，树突状细胞 (DC)、T 调节细胞 (Treg) 和 T 抑制细胞 (Ts) 亚群之间的干扰素γ (IFN-γ) 依赖性相互作用有助于同种异体移植物的接受。我们测量了 33 名血清肌酐 = 2.0 mg/dl 的肾移植受者的 DC 亚群、表达 Foxp3、Th1 或 Th2 细胞因子的 CD3(+)CD4(+)CD25(+)（Treg 表型）和 CD3(+)CD8(+)CD28(-)（Ts 表型）外周血淋巴细胞 (PBL)、外周 T 和 B 细胞计数以及血浆细胞因子移植后100多天。使用四色流式细胞术测量全血中的细胞亚群。与移植功能良好的患者相比，肌酐升高的患者 CD3(+)CD4(+)CD25(+)IFN-gamma(+) PBL 的检测频率较低 (P = 0.017)。在移植功能良好的患者中，CD3(+)CD4(+)CD25(+)IFN-γ(+) PBL 与高 Foxp3(+)、IL-2(+)、IL-12(+)、IL-4(+) 和 IL-10(+) CD3(+)CD4(+)CD25(+) T PBL 相关(P < 0.001)，低CD3(+)CD8(+)CD28(-)Foxp3(+) (P = 0.002)、CD3(+)CD4(+)DR(+) (P = 0.002)、CD3(+)CD8(+)DR(+) T (P = 0.005) 和 CD19(+) B PBL (P = 0.005) 和低谱系(-)HLA-DR(+)CD11c(+)CD123(-)DC1 (P = 0.006)。移植物功能受损的患者没有表现出这些关联。额外的流式细胞术分析证实CD4(+)CD25(+) PBL强烈共表达IFN-γ和Foxp3，特别是在移植功能良好的患者中。我们的数据支持CD3(+)CD4(+)CD25(+)Foxp3(+)IFN-gamma(+)细胞在具有良好移植接受性的移植受者亚组中的免疫调节作用。
There is evidence that interferon-gamma (IFN-gamma)-dependent interactions of dendritic cell (DC), T regulatory (Treg), and T suppressor (Ts) subpopulations contribute to allograft acceptance. We measured DC subsets, CD3(+)CD4(+)CD25(+) (Treg phenotype) and CD3(+)CD8(+)CD28(-) (Ts phenotype) peripheral blood lymphocytes (PBL) expressing Foxp3, Th1 or Th2 cytokines, peripheral T- and B-cell counts, and plasma cytokines in 33 kidney transplant recipients with a serum creatinine of = 2.0 mg/dl more than 100 days post-transplant. Cell subsets were measured in whole blood using four-color flow cytometry. Patients with increased creatinine had less frequently detectable CD3(+)CD4(+)CD25(+)IFN-gamma(+) PBL than patients with good graft function (P = 0.017). In patients with good graft function, CD3(+)CD4(+)CD25(+)IFN-gamma(+) PBL were associated with high Foxp3(+), IL-2(+), IL-12(+), IL-4(+), and IL-10(+) CD3(+)CD4(+)CD25(+) T PBL (P < 0.001), low CD3(+)CD8(+)CD28(-)Foxp3(+) (P = 0.002), CD3(+)CD4(+)DR(+) (P = 0.002), CD3(+)CD8(+)DR(+) T (P = 0.005) and CD19(+) B PBL (P = 0.005), and low lineage(-)HLA-DR(+)CD11c(+)CD123(-) DC1 (P = 0.006). Patients with impaired graft function did not show these associations. Additional flow cytometric analysis confirmed strong co-expression of IFN-gamma and Foxp3 by CD4(+)CD25(+) PBL particularly in patients with good graft function. Our data support an immunoregulatory role of CD3(+)CD4(+)CD25(+)Foxp3(+)IFN-gamma(+) cells in a subgroup of transplant recipients with good graft acceptance.