Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytes.
Mesenchymal stromal cells regulate immune cell function via the secretion of soluble factors. Cell membrane interactions between these cell types may play an additional role. Here, we demonstrate that subpopulations of allo-activated T cells are capable of binding to human adipose-derived stromal cells (ASC). The bound T-cell population contained CD8+ T cells and was enriched for CD4-CD8- T cells, whereas the proportion of CD4+ T cells was decreased compared with the non-bound T-cell population. Bound CD4+ T cells had high proliferative activity and increased CD25 and FoxP3 expression. However, they also expressed CD127, excluding regulatory T-cell function. In CD8+ T cells, IL-2 sensitivity, as determined by the analysis of phosphorylated STAT5, was lower in the presence of ASC and even lower in bound cells. In contrast, IL-2-induced phosphorylated STAT5 levels were higher in bound CD4+ T cells than in non-bound CD4+ T cells. Additionally, pro-proliferative TGF-beta signalling via endoglin and SMAD1/5/8 phosphorylation was detected in bound CD4+ T cells. Even after prolonged co-culture with ASC, the activated phenotype of bound CD4+ T cells persisted. In conclusion, these results demonstrate that the binding of lymphocytes to ASC represents an immunomodulatory mechanism in which CD8+ T cells are inhibited in their responsiveness to pro-inflammatory stimuli and reactive CD4+ T cells are depleted from the immune response.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Monique E
ME
Quaedackers
Carla C
CC
Baan
Willem
W
Weimar
Martin J
MJ
Hoogduijn
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D050799:STAT5 Transcription Factor / Q000378:metabolism; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C107514:SMAD9 protein, human; D050799:STAT5 Transcription Factor; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein