title: In vivo depletion of NKR-P1 positive cells in the recipient prior to small bowel transplantation enhances graft-versus-host disease (GvHD) in the rat.
abstract: Recent evidence for major histocompatibility complex (MHC) class I antigen-directed recognition mechanisms of natural killer cells (NKs) have revived interests in investigating non-adaptive immune responses in the framework of solid organ transplantation. A semi-allogeneic rat model of heterotopic small bowel transplantation (HSBTx) from male DA parental to male F1 hybrid rats (DA x LEW) was established to investigate the role of host NKs to attenuate graft-versus-host (GvH)-mediated immunosuppression and tissue injury. By use of anti-NKR-P1 monoclonal antibody (mAb) 3.2.3, host NKs were depleted effectively in vivo after triple intraperitoneal injection prior to HSBTx. In contrast to non-depleted animals, an initial lack of NK activity in F1 hosts significantly decreased the mean survival (P < 0.01) and substantially enhanced graft-versus-host disease (GvHD)-related damage to lymphoid and non-lymphoid target organs. These findings emphasize the important immunoregulatory role of host NKs during the early onset of GvHD.
authors.affiliation: Department of General and Thoracic Surgery, University of Kiel, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Fändrich
authors.forename: B
authors.initials: B
authors.lastname: Exner
authors.forename: A
authors.initials: A
authors.lastname: Papachrysanthou
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Jahnke
authors.forename: W H
authors.initials: WH
authors.lastname: Chambers
authors.forename: N
authors.initials: N
authors.lastname: Zavazava
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016516:CD4-CD8 Ratio; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D007421:Intestine, Small / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000502:physiology*; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000911:Antibodies, Monoclonal