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Blockade of osteopontin reduces alloreactive CD8 + T cell–mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang Shi, Yajun Guo, and Yanyun Zhang Blood Volume 117(5):1723-1733 February 3, 2011 ©2011 by American Society of Hematology

Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

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Page 1: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Blockade of osteopontin reduces alloreactive CD8+ T cell–mediated graft-versus-host disease

by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang Shi, Yajun Guo, and Yanyun Zhang

BloodVolume 117(5):1723-1733

February 3, 2011

©2011 by American Society of Hematology

Page 2: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Expression of OPN during GVHD. Lethally irradiated B6/SJL recipient mice (CD45.1+) were injected with C3H.SW CD8+ T cells (CD45.2+, 2 × 106) plus C3H.SW TCD BM (5 × 106) or C3H.SW

TCD BM (5 × 106) alone.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 3: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Inhibition of CD8+ T cell-mediated GVHD by anti-OPN Ab. Lethally irradiated B6/SJL recipient mice were injected with C3H.SW CD8+ T cells plus C3H.SW TCD BM or C3H.SW TCD BM alone.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 4: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Anti-OPN treatment reduces persistence of donor T cells in recipient tissues.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 5: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Effect of OPN on migration of donor-derived CD8+ T cells.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 6: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Anti-OPN Ab reduces donor T-cell survival.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 7: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Effects of OPN on T-cell activation.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology

Page 8: Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang

Maintenance of GVL on anti-OPN treatment.

Fang Zhao et al. Blood 2011;117:1723-1733

©2011 by American Society of Hematology