B7-H1 inhibits T cell proliferation through MHC class II in human mesenchymal stem cells.

Abstract

B7-H1 on mesenchymal stem cells (MSCs) is known to modulate immune response.

However, its expression pattern and exact immunomodulatory mechanism are unclear.

In this study, we examined the immunomodulatory mechanism through the expression

pattern of B7-H1 and major histocompatibility complex class II in various MSCs.

Human bone marrow, adipose tissue, and cord blood MSCs were isolated and

cultured. B7-H1, HLA-ABC, and HLA-DR expression on MSCs by interferon-gamma

(IFN-gamma) was detected time-dependently by flow cytometry. The inhibitory

effect of MSCs on T lymphocytes was observed in phytohemagglutinin

antigen-induced T cell proliferation assay. The expression of B7-H1 was rapidly

induced, but the expression of HLA-DR was induced at 48 hours after IFN-gamma

treatment. The inhibitory effect of MSCs on T cell proliferation could be

restored when the anti-B7-H1 monoclonal antibody was used to block the B7-H1, or

when the HLA-DRalpha small interfering RNA was used to interfere with its

expression. These results show that MSCs could inhibit the T cell proliferation

and activation by B7-H1 depending on the presence of HLA-DR. Therefore, MSCs

would have a strong effect on immune diseases such as graft-versus-host disease

and autoimmune diseases when MSCs are primed with IFN-gamma 48 hours before

transplantation.