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Updated: Jun 16, 2025

In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
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Trained immunity suppression determines kidney allograft survival.

Inge Jonkman1, Maaike M E Jacobs1, Yutaka Negishi2

  • 1Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|August 15, 2024
PubMed
Summary

Post-transplant serum from kidney recipients can suppress trained immunity, a key factor in immune response. This suppression is linked to better long-term kidney graft survival, suggesting a new therapeutic target.

Keywords:
graft survivalinnate immunitykidney transplantationtrained immunity

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Area of Science:

  • Immunology
  • Transplantation immunology
  • Innate immunity

Background:

  • The innate immune system is crucial for kidney transplant outcomes, but its precise role in long-term graft survival remains incompletely understood.
  • Trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells, enhances inflammatory responses to subsequent stimuli.
  • Understanding how innate immune cells influence kidney allograft survival is critical for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of trained immunity in kidney allograft survival.
  • To determine the impact of post-transplant serum from kidney transplant recipients on trained immunity.
  • To explore the potential of trained immunity as a therapeutic target for enhancing kidney graft survival.

Main Methods:

  • Peripheral blood mononuclear cells from healthy donors were stimulated in vitro to assess trained immunity.
  • Stimulation involved using pre-transplant and post-transplant serum from kidney transplant patients and immunosuppressive drugs.
  • Tumor necrosis factor and interleukin 6 cytokine levels were measured as readouts for trained immunity.

Main Results:

  • Serum collected from kidney transplant recipients one week post-transplantation demonstrated suppression of trained immunity.
  • A strong correlation was observed between the degree of trained immunity suppression by post-transplant serum and reduced rates of graft loss.
  • The suppressive effects of post-transplant serum are potentially mediated by novel actions of immunosuppressive drugs.

Conclusions:

  • Post-transplant serum possesses the capacity to suppress trained immunity in kidney transplant recipients.
  • Suppression of trained immunity by post-transplant serum is a significant predictor of long-term kidney graft survival.
  • Trained immunity emerges as a promising therapeutic target for optimizing immunosuppression and improving kidney transplant outcomes.