title: Circumvention of natural killer cell and T-cell mediated allogeneic target killing with tacrolimus (FK506) in small bowel transplantation related graft-vs-host disease.
abstract: The role of simultaneous donor-specific transfusion of unprocessed cellular bone marrow (BM) together with solid organ transplantation, a postulated concept to achieve long-term graft acceptance, was investigated in an experimental setting of semiallogeneic transplantation of parental small bowel (SBTx) to F1 hybrids. The established graft-vs-host (GvH) model revealed that simultaneous transfer of SB/BM substantially enhanced GvH-mediated immune responses in recipient target organs, e.g. skin, gut, and liver. In comparison to isolated SBTx, animal survival decreased from 16.1 (+/- 0.9) to 10.1 (+/- 0.8) days after additional BM transfusion, P < 0.001. Severe tissue injury of GvH-susceptible target organs in the setting of simultaneous SB and BMTx was associated with significant changes in recruitment and tissue distribution of NKR-P1+ cells during the GvH-related proliferative immune response. Tacrolimus effectively suppressed these initial events and prevented recipient animals from clinically and histologically observed damage caused by GvH disease.
authors.affiliation: Department of General and Thoracic Surgery, University of Kiel, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Fändrich
authors.forename: T
authors.initials: T
authors.lastname: Jahnke
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Exner
authors.forename: A
authors.initials: A
authors.lastname: Papachrysanthou
authors.forename: N
authors.initials: N
authors.lastname: Zavazava
mesh_terms: D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus