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 Blood, 15 October 2007, Vol. 110, No. 8, pp. 2803-2810.
Prepublished online as a Blood First Edition Paper on June 26, 2007; DOI 10.1182/blood-2006-11-055673.

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PLENARY PAPER

Prevention of graft-versus-host disease by anti–IL-7R{alpha} antibody

Brile Chung1, Eric P. Dudl2, Dullei Min1, Lora Barsky2, Nancy Smiley2, and Kenneth I. Weinberg1

1 Division of Stem Cell Transplantation, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA; 2 Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA

Graft-versus-host disease (GVHD) continues to be a serious complication that limits the success of allogeneic bone marrow transplantation (BMT). Using IL-7–deficient murine models, we have previously shown that IL-7 is necessary for the pathogenesis of GVHD. In the present study, we determined whether GVHD could be prevented by antibody-mediated blockade of IL-7 receptor {alpha} (IL-7R{alpha}) signaling. C57/BL6 (H2Kb) recipient mice were lethally irradiated and underwent cotransplantation with T-cell–depleted (TCD) BM and lymph node (LN) cells from allogeneic BALB/c (H2Kd) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti–IL-7R{alpha} antibody (100 µg per mouse per week) or PBS for 4 weeks. Anti–IL-7R{alpha} antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7R{alpha} blockade resulted in the reduction of donor CD4+ or CD8+ T cells in the periphery by day 30 after transplantation. Paradoxically, the inhibition of GVHD by anti–IL-7R{alpha} antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti–IL-7R{alpha} antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.


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Related Article in Blood Online:

IL-7: griffinesque role in GVHD
Pavan Reddy
Blood 2007 110: 2788. [Full Text] [PDF]





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