B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation.
B7-H4 has an inhibitory effect on immune responses via the down-regulation of T cell-mediated immunity, but how the engagement of B7-H4 molecules by counter molecules affects the signaling mechanism of the B7-H4-expressing cells is poorly defined. In this study, we found that B7-H4 expression was enhanced on B cells infected with Epstein-Barr virus (EBV) and that triggering of these molecules induced apoptosis of EBV-transformed B cells. Engagement of B7-H4 initially increased intracellular level of ROS, which then induced the expression of FasL. Engagement of B7-H4 subsequently provoked Fas-mediated and caspase-dependent apoptosis in association with cytochrome c and AIF, and EndoG was released from the mitochondria on EBV-transformed B cells. These results suggest that B7-H4 may be a potential therapeutic target for EBV involved malignancy diseases.
Song
Hyunkeun
H
Department of Anatomy and Tumor Immunology, Inje University College of Medicine, 633-165 Kaekum-2-dong, Jin-gu, Busan 614-735, Republic of Korea.
Park
Gabin
G
Kim
Yeong-Seok
YS
Hur
Indo
I
Kim
Hyunjin
H
Ryu
Jeoung Whan
JW
Lee
Hyun-Kyung
HK
Cho
Dae-Ho
DH
Choi
In-Hak
IH
Lee
Wang Jae
WJ
Hur
Dae Young
DY
D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018122:B7-1 Antigen / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D019014:fas Receptor / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D018122:B7-1 Antigen; D053222:Fas Ligand Protein; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D019014:fas Receptor; D045304:Cytochromes c; D020169:Caspases