The effects of preconditioning with IFN-γ, IL-4, and IL-10 on costimulatory ligand expressions of mesenchymal stem cells

INTRODUCTION: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells, and co-stimulation may play an important role in increasing the effects of MSCs on adaptive immune cells. Preconditioning may add to the effectiveness of MSCs. The aim of this study was to investigate alterations in the costimulatory ligand expressions of MSCs preconditioned with inflammatory cytokines.
METHODS: MSCs were preconditioned with interferon gamma (IFN-γ), interleukin (IL) 4 (IL-4), and IL-10, and changes in CD80, CD86, CD137L, CD252, CD274, CD275, and human leukocyte antigen (HLA) class I and II expressions were analyzed using flow cytometry and quantitative polymerase chain reaction methods. Human acute monocytic leukemia cell line (THP-1) macrophages preconditioned under the same conditions served as a control for comparison.
RESULTS: The frequencies of CD80 (p=0.0003), CD86 (p<0.0001), CD137L (p<0.0001), CD252 (p=0.0003), CD274 (p=0.0077), CD275 (p<0.0001), and HLA-II (p<0.0001) -positive MSCs was significantly lower than that of the THP-1 macrophages with either method, but there was no significant difference in the HLA-I (p=0.1506) cells. Comparison of the expression of the costimulatory ligands revealed that the expression of MSCs was significantly lower than that of THP-1 cells, and was not affected by cytokine stimuli.
DISCUSSION AND CONCLUSION: The study data indicated that although MSCs are strong immunomodulatory cells, the costimulatory ligand expression required for an effective antigen presentation was extremely low compared with that of professional antigen presenting cells. In addition, preconditioning with IFN-γ, IL-4, and IL-10 failed to increase the expression of important costimulatory ligands, such as CD80 and CD86, in MSCs. The stability of costimulatory ligand expression suggests that MSCs may be an effective source for HLA-I-mediated peripheral tolerance.