title: NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT.
abstract: In allogeneic hematopoietic stem cell transplantation (HSCT), controlling graft-versus-host disease (GVHD) while maintaining graft-versus-tumor (GVT) responses is of critical importance. Using a mouse model of allogeneic HSCT, we hereby demonstrate that NKG2D expression by CD8(+) T cells plays a major role in mediating GVHD and GVT effects by promoting the survival and cytotoxic function of CD8(+) T cells. The expression of NKG2D ligands was not induced persistently on normal tissues of allogeneic HSCT-recipient mice treated with anti-NKG2D antibody, suggesting that transient NKG2D blockade might be sufficient to attenuate GVHD and allow CD8(+) T cells to regain their GVT function. Indeed, short-term treatment with anti-NKG2D antibody restored GVT effects while maintaining an attenuated GVHD state. NKG2D expression was also detected on CD8(+) T cells from allogeneic HSCT patients and trended to be higher in those with active GVHD. Together, these data support a novel role for NKG2D expression by CD8(+) T cells during allogeneic HSCT, which could be potentially therapeutically exploited to separate GVHD from GVT effects.
authors: Department of Pathology and Laboratory Medicine.
authors: Mobin A
authors: MA
authors: Karimi
authors: Department of Pathology and Laboratory Medicine.
authors: Jerrod L
authors: JL
authors: Bryson
authors: Department of Medicine, and.
authors: Lee P
authors: LP
authors: Richman
authors: Department of Pathology and Laboratory Medicine.
authors: Andrew D
authors: AD
authors: Fesnak
authors: Department of Pathology and Laboratory Medicine.
authors: Theresa M
authors: TM
authors: Leichner
authors: Department of Pathology and Laboratory Medicine.
authors: Atsushi
authors: A
authors: Satake
authors: Department of Medicine, and Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and.
authors: Robert H
authors: RH
authors: Vonderheide
authors: Department of Molecular & Cell Biology, University of California, Berkeley CA.
authors: David H
authors: DH
authors: Raulet
authors: Department of Medicine, and.
authors: Ran
authors: R
authors: Reshef
authors: Department of Pathology and Laboratory Medicine.
authors: Taku
authors: T
authors: Kambayashi
mesh_terms: D064591:Allografts; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020350:Graft vs Tumor Effect / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K