Trained immunity in organ transplantation

Sep 28, 2019American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

Long-lasting immune memory in organ transplantation

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Trained immunity pathways are associated with graft loss in organ transplantation.

Donor-specific unresponsiveness without continuous immunosuppressive therapy remains challenging in organ transplantation.
Therapeutic approaches targeting the adaptive immune response have shown promise, yet long-term graft survival rates are still suboptimal.
Trained immunity involves nonpermanent changes in macrophages that enhance immune responses.
Trained macrophages increase costimulatory molecules and produce inflammatory signals that may drive organ rejection.
The review discusses how trained immunity contributes negatively to organ transplant outcomes and outlines related pathways.

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Consistent induction of donor-specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen-presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long-term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro-inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.

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Trained immunity in organ transplantation

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