Travers R L, Motta A C, Betts J A, Bouloumié A, Thompson D
Department for Health, University of Bath, Bath, UK.
Unilever R&D Vlaardingen, Vlaardingen, The Netherlands.
Int J Obes (Lond). 2015 May;39(5):762-9. doi: 10.1038/ijo.2014.195. Epub 2014 Nov 12.
BACKGROUND/OBJECTIVES: The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity.
SUBJECTS/METHODS: Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35-55 years with waist circumferences in lean (<94 cm), overweight (94-102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture.
Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants.
This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of potential compensatory mechanisms that may work to counteract adipose tissue inflammation, possibly through an increased number of T-regulatory cells.
背景/目的：人类脂肪组织中T淋巴细胞的存在直到最近才得到证实，对于它们在肥胖相关疾病发展中的潜在相关性知之甚少。我们旨在进一步表征这些细胞，特别是研究它们如何与常见超重和肥胖典型的适度增加的肥胖水平相互作用。
受试者/方法：从35 - 55岁健康男性中获取皮下脂肪组织和空腹血样，这些男性的腰围分别处于消瘦（<94厘米）、超重（94 - 102厘米）和肥胖（>102厘米）类别。通过基因表达和流式细胞术鉴定脂肪组织驻留的CD4 +和CD8 + T淋巴细胞以及巨噬细胞。通过活化标志物CD25和CD69的表达进一步表征T淋巴细胞。使用基因表达分析和组织培养研究脂肪组织炎症。
参与者反映了从消瘦到I类肥胖的一系列肥胖程度。随着肥胖水平的增加，皮下脂肪组织中CD4（辅助性T细胞）和CD68（巨噬细胞）以及FOXP3 RNA转录本的表达升高（分别为P<0.001、P<0.001和P = 0.018）。流式细胞术显示腰围与活化的脂肪组织驻留CD4 +和CD8 + T淋巴细胞上每个细胞的CD25和CD69表达水平之间存在显著相关性（P值范围从0.053至<0.001）。与血液T淋巴细胞未发现此类关系。这种T淋巴细胞活化增加与皮下全脂肪组织外植体中各种促炎和抗炎细胞因子的表达和分泌增加有关。
这是第一项证明即使适度的超重/肥胖也会引起脂肪组织免疫功能改变的研究。我们的结果强调了T淋巴细胞在脂肪组织扩张过程中的重要性，以及可能存在的潜在补偿机制，这些机制可能通过增加调节性T细胞数量来对抗脂肪组织炎症。
