Submitted November 2, 2006
Accepted June 4, 2007
Prevention of graft-versus-host disease by anti-IL-7R
antibody
Brile Chung, Eric P Dudl, Dullei Min, Lora Barsky, Nancy Smiley, and Kenneth I Weinberg*
Pediatrics Division of Stem Cell Transplantation, Stanford University, Stanford, CA, United States
Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA, United States
* Corresponding author; email: kw1{at}stanford.edu.
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 
(IL-7R) signaling. C57/BL6 (H2Kb) recipient mice were lethally irradiated and co-transplanted 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 antibody (100 µg/mouse/week) or PBS for 4 weeks. Anti-IL-7R antibody treatment significantly decreased GVHD-related morbidity and mortality, compared to placebo (30% to 80%). IL-7R blockade resulted in the reduction of donor CD4+ or CD8+ T cells in the periphery by day 30 post-transplantation. Paradoxically, the inhibition of GVHD by anti-IL-7R antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7R antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T cell reconstitution.
