Association of Higher CD4+CD25highCD127low, FoxP3+, and IL‐2+ T Cell Frequencies Early After Lung Transplantation With Less Chronic Lung Allograft Dysfunction at Two Years
Association of Higher CD4+CD25highCD127low, FoxP3+, and IL‐2+ T Cell Frequencies Early After Lung Transplantation With Less Chronic Lung Allograft Dysfunction at Two Years
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DOI：
10.1111/ajt.14148
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发表时间：
2017-06
影响因子：
8.8
通讯作者：
J. Salman;F. Ius;A. Knoefel;W. Sommer;T. Siemeni;Christian Kuehn;I. Tudorache;M. Avşar;Tomoyuki Nakagiri;G. Preissler;RA Hatz;M. Greer;Tobias Welte;A. Haverich;G. Warnecke
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文献类型：
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作者：
J. Salman;F. Ius;A. Knoefel;W. Sommer;T. Siemeni;Christian Kuehn;I. Tudorache;M. Avşar;Tomoyuki Nakagiri;G. Preissler;RA Hatz;M. Greer;Tobias Welte;A. Haverich;G. Warnecke
调节性 T 细胞 (Treg) 可以调节同种异体抗原，并可能抵消肺移植中的慢性肺同种异体移植功能障碍 (CLAD)。我们前瞻性地分析了外周血中的 Treg，并将亚群百分比与 2 年 CLAD 的发病率相关联。在 2009 年 1 月至 2011 年 7 月期间进行肺移植的患者中，只有具有足够 Treg 测量值的患者才被纳入研究。在肺移植前、移植后 3 周以及 3、6、12 和 24 个月时测量 Tregs，将其定义为 CD4+CD25high T 细胞，并进一步分析 CTLA4、CD127、FoxP3 和 IL-2 表达。 2009年1月至2011年7月期间，我们机构共完成了264名患者的移植手术。在纳入研究的 138 名患者（52%）中，31 名患者（22%）在移植后 2 年内出现 CLAD。肺移植后 3 周，Treg 频率与随后的 CLAD 缺失之间检测到统计学上显着的正相关。在多变量分析中，肺移植后 3 周时 CD4+CD25highCD127low、CD4+CD25highFoxP3+ 和 CD4+CD25highIL-2+ T 细胞频率的增加成为 2 年 CLAD 发展的保护因素。总之，肺移植后早期特定 Treg 亚群的较高频率可预防 CLAD 的发展。
Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung‐transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12, and 24 months after transplantation and were defined as CD4+CD25high T cells and further analyzed for CTLA4, CD127, FoxP3, and IL‐2 expressions. Between January 2009 and July 2011, 264 patients were transplanted at our institution. Among the 138 (52%) patients included into the study, 31 (22%) developed CLAD within 2 years after transplantation. As soon as 3 weeks after lung transplantation, a statistically significant positive association was detected between Treg frequencies and later absence of CLAD. At the multivariate analysis, increasing frequencies of CD4+CD25highCD127low, CD4+CD25highFoxP3+ and CD4+CD25highIL‐2+ T cells at 3 weeks after lung transplantation emerged as protective factors against development of CLAD at 2 years. In conclusion, higher frequencies of specific Treg subpopulations early after lung transplantation are protective against CLAD development.