The impact of adiposity on adipose tissue-resident lymphocyte activation in humans.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Department for Health, University of Bath, Bath, UK.
R L
RL
Travers
Unilever R&D Vlaardingen, Vlaardingen, The Netherlands.
A C
AC
Motta
Department for Health, University of Bath, Bath, UK.
J A
JA
Betts
INSERM U1048, Institut des maladies métaboliques et cardiovasculaires and Université Paul Sabatier, Toulouse, France.
A
A
Bouloumié
Department for Health, University of Bath, Bath, UK.
D
D
Thompson
D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000276:immunology* / Q000502:physiology; D000328:Adult; D001823:Body Composition; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000378:metabolism* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*