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Am. J. Respir. Crit. Care Med., Volume 159, Number 1, January 1999, 199-205

Mixed Hematopoietic Chimerism Induces Donor-specific Tolerance for Lung Allografts in Rodents

SI M. PHAM, SURINDRA N. MITRUKA, WOOK YOUM, SEN LI, NOBUYOSHI KAWAHARADA, SAMUEL A. YOUSEM, YOLONDA L. COLSON, and SUZANNE T. ILDSTAD

Departments of Surgery and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Institute for Cellular Therapeutics, Allegheny University of Health Sciences, Philadelphia, Pennsylvania

Mixed hematopoietic chimerism is a state in which bone marrow hematopoietic stem cells from two genetically different animals coexist. We investigated whether mixed hematopoietic chimerism, resulting from the transplantation of host and donor bone marrow into a lethally irradiated rat, would confer donor-specific tolerance to lung allografts. Recipient rats (Fisher or or Wistar Furth [WF]) were irradiated (1,100 cGy) and reconstituted with a mixture of T-cell-depleted syngeneic plus allogeneic bone marrow. After mixed chimerism was documented by the presence of donor- and host-derived cells in the peripheral blood 4 wk after bone marrow reconstitution, mixed chimeras underwent orthotopic left lung transplantation with donor-specific and third-party lung allografts. No immunosuppressive agents were administered after lung transplantation. All donor-specific lung allografts were accepted by mixed chimeras (n = 40), while all third-party grafts (n = 7) were rejected within 10 d, a time course similar to that for grafts transplanted into naive recipients (n = 14). Radiation control recipients (n = 7) who did not develop mixed chimerism because the donor bone marrow had failed to engraft, also rejected donor-specific grafts within 10 d. We conclude that mixed hematopoietic chimerism induces donor-specific transplantation tolerance to lung allografts.




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Copyright © 1999 American Thoracic Society 		  ATS 2008 State of the Art Course