Spontaneous acceptance of grafts can be hightlighted by novel mechanisms of drug-free transplantation tolerance. Several animal studies showed that mouse renal allografts in certain strain combinations and rat liver transplants can promote acceptance without immunosuppression. We also identified that rodent islet allografts from B cell-deficient donors have a remarkable ability to promote across fully MHC mismatched B cell-deficient recipients. All wild-type Balb/c islets into B cell-deficient ¯o;MT-/- B6 recipients and B cell-deficient JH islet into wild-type B6 recipients were rejected by 20 days post transplantation. Strikingly, the islet allograft from JH mice survived long-term in 5 out of 6 ¯o;MT-/- B6 recipients without treatment. Adoptive transfer of donor B cells caused allograft rejection quickly in all ¯o;MT-/- B6 recipients bearing JH islets, but this effect was not observed in the recipient B cell transferred recipients suggesting donor B cells is more pathogenic in early immune processes of mouse islet rejection compared to recipients B cells. Interestingly, flow cytometry analysis showed that significantly increased portion of plasmacytoid dendritic cells (pDC) in isolated islets, spleens and bone marrow from B cell-deficient mice compared to wild-type mice. Moreover, adoptive transfer of pDC purified from JH mice suppressed allograft rejection upon transfer to untreated ¯o;MT-/- B6 secondary host received Balb/c islets suggesting tolerogenic effect of donor pDC. These results demonstrate that donor islets include cellular populations exerting contradictory roles: B cells represent critical players in the pathogenesis of graft rejection and pDCs contribute to tolerance. This study will help developing novel therapies targeting donor B cells and pDC to induce indefinite transplant survival.

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