Intrathymic inoculation of donor bone marrow induces long-term acceptance of lung allografts.
BACKGROUND
We investigated whether intrathymic inoculation of donor bone marrow at the time of transplantation induced long-term acceptance of lung allografts.


METHODS
Four- to-six-week-old August Copenhagen Irish (ACI) and Wistar Furth (WF) rats were used as donors and recipients, respectively. After being inoculated intrathymically with either donor-specific (ACI) or third-party (F344) bone marrow (2.0 x 10(7) cells/lobe), the recipient (WF) animal received a left lung transplant from an ACI donor. A short course of tacrolimus (1 mg/kg per day for 5 days) was administered. Animals were sacrificed at timed intervals after transplantation, and rejection was graded on a scale of 0 (none) to 4 (severe).


RESULTS
At 28 days, animals receiving donor-specific bone marrow have lower (p < 0.01) median rejection grade (MRG = 0.25; n = 6) than those receiving third-party bone marrow (MRG = 3; n = 6) and controls (no bone marrow; MRG = 2.5; n = 6). Animals receiving intrathymic donor bone marrow accepted lung allografts up to 380 days with minimal rejection (MRG = 2; n = 6). Long-term lung recipients also accepted a challenging donor-specific heart graft (n = 4) for more than 150 days. In mixed lymphocyte reaction assays, T lymphocytes of WF recipients that had received intrathymic bone marrow (from ACI donor) exhibited low response (similar to self antigens) to donor (ACI) cells, but reacted strongly (five times higher) to third-party (F344) cells.


CONCLUSIONS
Intrathymic inoculation of donor bone marrow at the time of transplantation along with a short course of tacrolimus induces long-term acceptance of lung allografts in rats. This simple approach of tolerance induction may have clinical application.
Li
Sen
S
Division of Cardiothoracic Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA.
Louis
Louis B
LB
Kawaharada
Nobuyoshi
N
Yousem
Samuel A
SA
Pham
Si M
SM
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection; D007108:Immune Tolerance / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D016559:Tacrolimus / Q000494:pharmacology; D013950:Thymus Gland; D014184:Transplantation, Homologous
D016559:Tacrolimus