Mixed hematopoietic chimerism induces donor-specific tolerance for lung allografts in rodents

• Published in: American journal of respiratory and critical care medicine Vol. 159; no. 1; pp. 199 - 205
• Main Authors: PHAM, S. M, MITRUKA, S. N, WOOK YOUM, SEN LI, KAWAHARADA, N, YOUSEM, S. A, COLSON, Y. L, ILDSTAD, S. T
• Format: Journal Article
• Language: English
• Published: New York, NY American Lung Association 1999
• Subjects: Animals; Biological and medical sciences; Chimera - physiology; Graft Survival - physiology; Hematopoietic Stem Cells - physiology; Immune Tolerance - physiology; Lung - pathology; Lung Transplantation; Male; Medical sciences; Radiography, Thoracic; Rats; Rats, Inbred Strains; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the respiratory system; Time Factors; Tissue Donors; Transplantation, Homologous; Immunopathology; Rat; Stem cell; Lung; Rodentia; Hematopoietic cell; Graft versus host reaction; Transplantation; Recipient; Experimental study; Homotransplantation; Prevention; Vertebrata; Mammalia; Donor; Surgery; Animal; Immune tolerance; Complication; Mixed lineage; Technique; Chimera
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.159.1.9712041

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.