caa a22 4500 477036031 CHVBK 20180405111305.0 cr unu---uuuuu 170330e19961001xx s 000 0 eng 10.1007/s002689900159 doi (NATIONALLICENCE)springer-10.1007/s002689900159 Correlation between Graft-Versus-Host Induced Immunosuppression and Host Natural Killer Cell Activity in Small Bowel Transplantation [Elektronische Daten] [Fred Fändrich, Jörg Schröder, Beate Exner, Athanasios Papachrysanthou, Jochen Peters, William Chambers, Nicholas Zavazava] Abstract. The occurrence of graft-versus-host disease (GvHD) following small bowel transplantation (SBTx) can be tuned by the recipient's initial natural killer (NK) cell activity, which modifies the immunogeneic balance between donor and host immunocompetent cells. This study was aimed to investigate the role of host NK cells on the incidence and severity of GvHD following SBTx. Intraperitoneal administration of 50 μl ascites fluid of the highly specific anti-NKR-P1 monoclonal antibody (mAb) 3.2.3 into F1 recipient animals on three consecutive days prior to SBTx was performed to suppress NK activity in F1 hybrids. In vivo treatment with 3.2.3 mAb effectively depleted recipient NK activitiy for at least 10 days in spleens and mesenteric lymph nodes of F1 hosts. In contrast to nontreated F1 recipients, all 3.2.3 mAb-pretreated F1 animals suffered from severe signs of GvHD, and the mean survival time was decreased significantly from 16.0 ± 0.9 days to 11.0 ± 0.8 days (: p < 0.01) in nontreated and NKR-P1-depleted F1 animals, respectively. Other sequelae included earlier onset of GvH manifestations, pronounced damage of primary and secondary lymphatic organs, substantial increase in spleen index, and lower CD4 + /CD8 + ratios over the course of progressing GvHD. Our results underline the important immunoregulatory role of NK cells as a first defensive line acting on the alloreactivity of donor-derived immunocompetent cells in this model of solid organ transplantation. 1996 by the Société Internationale de Chir, ugie Fändrich Fred Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Schröder Jörg Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Exner Beate Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Papachrysanthou Athanasios Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Peters Jochen Institute of Pathology, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Chambers William Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, U.S.A., US aut Zavazava Nicholas Institute of Immunology, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut https://doi.org/10.1007/s002689900159 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002689900159 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fändrich Fred Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut NATIONALLICENCE 700 1- Schröder Jörg Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut NATIONALLICENCE 700 1- Exner Beate Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut NATIONALLICENCE 700 1- Papachrysanthou Athanasios Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut NATIONALLICENCE 700 1- Peters Jochen Institute of Pathology, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut NATIONALLICENCE 700 1- Chambers William Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, U.S.A., US aut NATIONALLICENCE 700 1- Zavazava Nicholas Institute of Immunology, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer