Adipose-derived stromal cell immunosuppression of T cells is enhanced under "physiological" hypoxia

Multipotent mesenchymal stromal cells (MSCs) are characterized by immunomodulatory properties along with the high proliferative and paracrine activity, as well as multilineage potency. The effects of MSCs on the T cell adaptive immunity are of a special interest. Low O₂ level (1-7 %) is known to be typical for the putative site of the MSC - T cell interactions. A comparative evaluation of the effects of adipose tissue derived MSC (ASCs) on the mitogen-stimulated T cells at the ambient (20 %) and tissue-related (5 %) O₂ levels demonstrated reduced T cell activation by the HLA-DR expression, decreased pro-inflammatory and increased anti-inflammatory cytokine production in co-culture, inhibited T cell proliferation, with the effects increased at hypoxia. T cell interactions with ASCs resulted in the up-regulation of PDCD1, Foxp3, and TGFβ1 known to play an important role in the immune response suppression, and in the down-regulation of genes involved in the inflammatory reaction (IL2, IFNG). These changes were significantly increased under hypoxia. At the same time, neither ASCs nor the reduced O₂ level had negative effects on the viability of T cells.