Mechanisms of Mixed Chimerism-Based Transplant Tolerance

Trends Immunol. 2017 Nov;38(11):829-843. doi: 10.1016/j.it.2017.07.008. Epub 2017 Aug 18.

Abstract

Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells. Here we review recent mechanistic insights into tolerance and the development of more robust and safer protocols for tolerance induction that will be guided by innovative immune monitoring tools.

Keywords: clonal deletion; mixed chimerism; regulatory T cells; tolerance.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Chimerism*
  • Clonal Deletion
  • Humans
  • Kidney Transplantation
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation Chimera
  • Transplantation Conditioning / methods*
  • Transplantation Immunology*
  • Transplantation Tolerance*