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Right arrow Lung - transplantation

Ann Thorac Surg 2003;75:257-263
© 2003 The Society of Thoracic Surgeons

Original article: general thoracic

Intrathymic inoculation of donor bone marrow induces long-term acceptance of lung allografts

Sen Li, MDa, Louis B. Louis, IV, MDa, Nobuyoshi Kawaharada, MD, PhDb, Samuel A. Yousem, MDc, Si M. Pham, MDa*

a Division of Cardiothoracic Surgery, University of Miami School of Medicine, Miami, Florida,, USA
b Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
c Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Accepted for publication August 9, 2002.

* Address reprint requests to Dr Pham, Division of Cardiothoracic Surgery, University of Miami School of Medicine, Highland Professional Building, 5th Floor, 1801 NW 9th Ave, Miami, FL 33136, USA.
e-mail: spham{at}med.miami.edu

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.

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 107 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.






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