Induction with T-cell receptor antibody leads to long-term laryngeal allograft function.
OBJECTIVE
The use of induction therapy with alphabeta T-cell receptor (alphabetaTCR) monoclonal antibody in association with tacrolimus in an allogeneic rat laryngeal transplant model permits rigorous long-term evaluation of potential short-term synergism offered by these agents.


METHODS
The allogeneic model consisted of 19 Brown Norway larynges transplanted to Lewis recipients. Treatment consisted of tacrolimus (1.2 mg/kg per day) alone and in combination with 7 days of alphabetaTCR (0.5 mL/d). Control groups consisted of untreated animals, as well as a semiallogeneic model with Lewis-Brown Norway larynges transplanted to Lewis recipients and treated with tacrolimus monotherapy. Each group consisted of 6 to 11 rats. The median duration of engraftment was 44 days (range, 14-106 days). Graft histopathology was graded according to an established 31-point scale in a blinded fashion. Long-term grafts (>75 days) were followed with serum parathyroid hormone levels.


RESULTS
Untreated controls experienced almost complete rejection (mean score, 27; SD, 0). Allogeneic transplants treated with tacrolimus monotherapy experienced near-complete rejection (mean score, 25.2; SD, 2.1). Allogeneic transplants treated with combination therapy and followed for a median duration of 100 days demonstrated significantly better rejection scores than controls (mean score, 11.1; SD, 1.7; P = .003). Combination therapy was also significantly more effective in preventing acute rejection than monotherapy with tacrolimus in a semiallogeneic model (mean score, 22.1; SD, 4.6; P < .04).


CONCLUSIONS
Induction therapy with tacrolimus and alphabetaTCR prevents rejection in an allogeneic model for up to 100 days. This regimen was associated with significantly better histopathologic rejection scores than untreated controls, or monotherapy with tacrolimus in allogeneic or semiallogeneic models.
Knott
P Daniel
PD
The Head and Neck Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. knottp@ccf.org
Dan
Olivia
O
Strome
Marshall
M
D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D007830:Larynx / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D011300:Preoperative Care; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage*; D012016:Reference Values; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016559:Tacrolimus