Accommodation in Allogeneic and Xenogeneic Organ Transplantation: Prevalence, Impact, and Implications for Monitoring and for Therapeutics

Accommodation refers to acquired resistance of organs or tissues to immune or inflammatory reactions that might otherwise cause severe injury or rejection. As first observed in ABO-incompatible kidney transplants and heterotopic cardiac xenografts, accommodation was identified when organ transplants continued to function despite the presence of anti-graft antibodies and/or other reactants in the blood of recipients. Recent evidence suggests many and perhaps most organ transplants have accommodation, as most recipients mount B cell responses specific for the graft. Wide interest in the impact of graft-specific antibodies on the outcomes of transplants prompts questions about which mechanisms confer protection against such antibodies, how accommodation might be detected and whether and how rejection could be superimposed on accommodation. Xenotransplantation offers a unique opportunity to address these questions because immune responses to xenografts are easily detected and the pathogenic impact of immune responses is so severe. Xenotransplantation also provides a compelling need to apply these and other insights to decrease the intensity and toxicity of immunosuppression that otherwise could limit clinical application.