Metastable tolerance in nonhuman primates and humans.

Area of Science:

• Transplantation immunology
• Immunology
• Cellular immunology

Background:

• Allogeneic organ transplant recipients can often forego immunosuppression for extended periods before rejection.
• Immune cell depletion, especially lymphocyte depletion, is a successful strategy for inducing transplant tolerance.

Purpose of the Study:

• To explore the mechanisms of metastable tolerance in organ transplantation.
• To identify potential biomarkers for monitoring transplant tolerance.

Main Methods:

• Review of nonhuman primate and human studies on organ transplantation and immune responses.
• Analysis of the role of regulatory T cells (Tregs) in donor-specific tolerance.
• Investigation of the involvement of transforming growth factor-beta (TGF-β) and interleukin-10 in Treg-mediated suppression.

Main Results:

• Metastable tolerance develops over time in a donor-specific fashion, primarily mediated by donor antigen-specific regulatory T cells.
• CD8+ and CD4+ T-regulatory cells suppress effector T cells via TGF-β or IL-10.
• CD4+ TGF-β(latent) T-cell infiltrates may serve as a diagnostic marker for metastable tolerance, with their loss correlating to tolerance loss.

Conclusions:

• Donor-specific regulatory T cells play a crucial role in achieving and maintaining transplant tolerance.
• Diagnostic tools for monitoring regulatory T cells are essential for future immunosuppressive drug withdrawal protocols.
• Understanding these mechanisms is key to overcoming challenges in clinical transplantation tolerance.