Circumvention of natural killer cell and T-cell mediated allogeneic target killing with tacrolimus (FK506) in small bowel transplantation related graft-vs-host disease.
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.
Fändrich
F
F
Department of General and Thoracic Surgery, University of Kiel, Germany.
Jahnke
T
T
Peters
J
J
Exner
B
B
Papachrysanthou
A
A
Zavazava
N
N
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*
D007166:Immunosuppressive Agents; D016559:Tacrolimus