The complement system developed early in our evolutionary past as a protein-based method for targeting and destroying pathogens. Organ transplantation is a relatively new procedure, with the first successful kidney transplant occurring in 1954. However, this “old player” continues to have important implications for our “new tricks”, according to a recent article by Llaudo et al published in the American Journal of Transplantation which identified a role for a complement receptor in heart transplant rejection.
In mice, the long-term survival of heart transplants was previously demonstrated to depend upon the accumulation within the graft of an immunosuppressive blood cell population known as regulatory myeloid cells (Mregs), which prolong graft survival by promoting the expansion of anti-inflammatory regulatory T cells (Tregs) and inhibiting the activity of damaging effector T cells (Teffs). Llaudo et al took this finding a step further, showing that Mregs lacking expression of the receptor for complement protein C5a (C5aR1) are not capable of migrating to the heart allograft, causing rejection to occur more quickly.
This finding contributes to our understanding of mechanisms regulating the development of an immunosuppressive intragraft microenvironment following the treatment of heart transplant recipients with costimulation-blockade therapy. Future studies will continue to enhance our knowledge of immunological tolerance and perhaps one day permit total graft acceptance.
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Llaudo I, Fribourg M, Medof ME, et al. (2019) C5aR1 regulates migration of suppressive myeloid cells required for costimulatory blockade‐induced murine allograft survival. American Journal of Transplantation, 19(3):633-645. https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.15072