17595335

pubmed:Citation

8

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-7Ralpha) signaling. C57/BL6 (H2K(b)) recipient mice were lethally irradiated and underwent cotransplantation with T-cell-depleted (TCD) BM and lymph node (LN) cells from allogeneic BALB/c (H2K(d)) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti-IL-7Ralpha antibody (100 mug per mouse per week) or PBS for 4 weeks. Anti-IL-7Ralpha antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7Ralpha 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-7Ralpha antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7Ralpha antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.

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http://linkedlifedata.com/resource/pubmed/journal/7603509

http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-7, http://linkedlifedata.com/resource/pubmed/chemical/interleukin-7 receptor, alpha chain

Oct

pubmed-author:BarskyLoraL, pubmed-author:ChungBrileB, pubmed-author:DudlEric PEP, pubmed-author:MinDulleiD, pubmed-author:SmileyNancyN, pubmed-author:WeinbergKenneth IKI

15

NLM

2803-10

pubmed-meshheading:17595335-Animals, pubmed-meshheading:17595335-Antibodies, Monoclonal, pubmed-meshheading:17595335-Antibody Formation, pubmed-meshheading:17595335-Bone Marrow Transplantation, pubmed-meshheading:17595335-Female, pubmed-meshheading:17595335-Graft vs Host Disease, pubmed-meshheading:17595335-Immunophenotyping, pubmed-meshheading:17595335-Male, pubmed-meshheading:17595335-Mice, pubmed-meshheading:17595335-Mice, Mutant Strains, pubmed-meshheading:17595335-Receptors, Interleukin-7, pubmed-meshheading:17595335-T-Lymphocytes, pubmed-meshheading:17595335-Thymus Gland, pubmed-meshheading:17595335-Transplantation, Homologous

Prevention of graft-versus-host disease by anti IL-7Ralpha antibody.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural