The negative co-signaling molecule b7-h4 is expressed by human bone marrow-derived mesenchymal stem cells and mediates its T-cell modulatory activity.
Though experimental evidence shows that human bone marrow-derived mesenchymal stem cells (hBMSCs) are able to suppress T-cell activation and proliferation, the precise mechanisms are still not completely understood. Here, we investigated the role of the negative costimulatory molecule B7-H4 in the immunosuppressive effect of hBMSCs on T-cell activation. We showed that B7-H4 expresses abundantly on hBMSCs assessed by reverse transcription, immunofluorescence staining, and flow cytometric analysis. Further studies demonstrated that B7-H4 expressed on hBMSCs inhibits T-cell activation and proliferation via induction of cell cycle arrest and inhibition of NF-kappaB nuclear translocation. Blocking B7-H4 would decrease the secretion of transforming growth factor-beta1 (TGF-beta1) in the supernatant of activated T cells co-cultured with hBMSCs. Addition of neutralizing antibodies against B7-H4 significantly attenuated the inhibitory effects of hBMSCs on T-cells. Thus, our study established the novel role of B7-H4 molecule in the suppressive effect of hBMSCs on T-cell activation and proliferation. Taken together, these results highlight the complex role of hBMSCs in regulating the immune response, asserting the possibility of their therapeutic application in transplantation, the treatment of graft-versus-host disease (GVHD), and autoimmune diseases.
Xue
Qun
Q
Clinical Immunology Key Lab of Jiangsu Province, First Affiliated Hospital of Suzhou University, People's Republic of China.
Luan
Xi-Ying
XY
Gu
Yan-Zheng
YZ
Wu
Hong-Ya
HY
Zhang
Guang-Bo
GB
Yu
Ge-Hua
GH
Zhu
Hua-Ting
HT
Wang
Mingyuan
M
Dong
Wanli
W
Geng
Yong-Jian
YJ
Zhang
Xue-Guang
XG
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human