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Overlap between Alloimmunity and Autoimmunity in the Rat and Human: Evidence for Important Contributions for Dendritic and Regulatory Cells

Noriko Murase, MD

Pittsburgh Transplantation Institute and the University of Pittsburgh

Conor P. Delaney, MD, PhD

Cleveland Clinic Foundation

Alloimmunity and autoimmunity share a number of important afferent, effector, and regulatory immunological pathways. It is likely that they also share overlapping specificities that at least partially explain the ability of allograft rejection to trigger autoimmune responses, the increased susceptibility of patients with autoimmune diseases to allograft rejection, and a strikingly similar histopathologic appearance of acute and chronic rejection to some organ-specific autoimmune diseases. Clinical and experimental data are presented and reviewed, showing some overlapping specificities of effector and regulatory mechanisms during alloimmunity and autoimmunity. The speculation is made that tissue damage during acute rejection uncovers self-reactive T cell clones via the process of epitope spreading, perhaps mediated by heat-shock-protein-peptide complex-priming of recipient dendritic cells. Conversely, donor dendritic cells are suggested as a candidate for stimulating regulatory T cells that help maintain allograft acceptance in the periphery.

Key Words: autoimmunity • alloimmunity • immune regulation • dendritic cells

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