B7-H1 up-regulation on dendritic-like leukemia cells suppresses T cell immune function through modulation of IL-10/IL-12 production and generation of Treg cells.
Dendritic-like leukemia cells (DLLC) originating from leukemic cells could potentially induce a T cell-mediated anti-leukemia immune response. It has been demonstrated that B7-H1, a newly identified homologue of CD80/CD86, is abundant in human carcinomas and dendritic cells (DC), can exert co-stimulatory and immune regulatory functions. We demonstrated that B7-H1 was significantly expressed on AML cells and was strongly enhanced after differentiation to DLLC. Blockade of B7-H1 expressed on DLLC results in increased T cell proliferation and Th1 cytokine production, and decreased Th2 cytokine production. Importantly, autologous CTLs induced by DLLC treated with B7-H1 mAb showed significantly increased specific cytotoxcity against AML blasts. We further demonstrated that a significant decrease in IL-12 production, increase in IL-10 production by DLLC, and an increased CD4(+)CD25(+)Foxp3(+) T regulatory population lead to the defective T cell immune response that is induced by B7-H1 up-regulation on DLLC. Our data suggest that up-regulated B7-H1 on DLLC acts as a strong inhibitor of anti-leukemia T cell response, and that blockade of B7-H1 can improve DLLC-mediated anti-leukemia immunity.
Ge
Wei
W
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China.
Ma
Xiaotong
X
Li
Xin
X
Wang
Yafei
Y
Li
Changhong
C
Meng
Hengxing
H
Liu
Xiaofan
X
Yu
Zhen
Z
You
Shengguo
S
Qiu
Lugui
L
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D060890:B7-H1 Antigen; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12