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

Abstract

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.

Long-Term Observation After Simultaneous Lung and Intra–Bone Marrow–Bone Marrow Transplantation

“…They have also reported that mixed hematopoietic chimerism induces donor-specific tolerance for lung allografts in rats. 5 In their study, they prepared mixed chimeric rats, in which T cell-depleted syngeneic plus donor BMCs were transplanted into irradiated recipients; 4 weeks later, lung transplantation was carried out. However, it would be difficult to apply this method to clinical lung transplantation from cadavers.…”

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets

“…In addition, we have recently shown the same findings in the transplantation of combinations of BMCs and other organs or tissue (such as the skin, leg and lung 18,[37][38][39] as in PI transplantation. Pham et al 40 and Foster et al 41 have also shown the importance of the existence of donor hematopoietic cells for the acceptance of the lung and composite tissue in the transplantation of the combination of BMCs and organs. The absence of a response of T cells in the PI-accepting rats to both recipient and donor MHC determinants in MLR suggests the induction of tolerance in the PI-accepting rats, resulting in long-term acceptance of the grafted PIs without the use of immunosuppressants.…”

Obliterative bronchiolitis or chronic lung allograft rejection: A basic science review

“…Lethally irradiated rats reconstituted with chimeric T-cell-depleted syngeneic and allogeneic bone marrow accepted orthotopic lung and heterotopic tracheal transplants indefinitely, with minimal histopathologic evidence of rejection. 46,47 In 1 clinical series, increased peripheral-blood allogeneic microchimerism correlated with freedom from OB. 48…”