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.