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Blood. 2005 Jul 15;106(2):749-55. Epub 2005 Mar 29.

Critical role of host gammadelta T cells in experimental acute graft-versus-host disease.

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  • 1Department of Internal Medicine, 6310 CCGC, University of Michigan Cancer Center, 1500 East Medical Center Dr, Ann Arbor, MI 48109-0942, USA.

Abstract

Gammadelta T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host gammadelta T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host gammadelta T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) gammadelta monoclonal antibody reduced GVHD, and gammadelta T-cell-deficient (gammadelta-/-) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P < .001). gammadelta T cells were responsible for this difference because reconstitution of gammadelta-/- recipients with gammadelta T cells restored GVHD mortality. gammadelta-/- recipients showed decreased serum levels of tumor necrosis factor alpha (TNF-alpha), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from gammadelta-/- recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with gammadelta T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon gamma (IFN-gamma), TNF-alpha, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host gammadelta T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells.

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PMID:
15797996
[PubMed - indexed for MEDLINE]
PMCID:
PMC1895173
Free PMC Article
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