title: Prospects for therapeutic tolerance in humans.
abstract: OBJECTIVE
  To provide an overview of recent advances and future possibilities for therapeutic tolerance.
  
  
  RESULTS
  Allograft survival despite complete immunosuppressant withdrawal has been demonstrated in selected renal-transplant recipients with haematopoietic chimerism. Early clinical trials of mesenchymal stromal cell therapy have shown promising results in several autoimmune diseases. Regulatory T cells show potential benefit in graft versus host disease, although challenges to ex-vivo expansion remain. Targeted modulation of T-cell function in vivo with monoclonal antibodies has shown beneficial effects in phase II/III trials of multiple sclerosis (alemtuzumab) and type I diabetes mellitus (teplizumab, otelixizumab). Emerging data from animal models suggest an important role for the commensal microbiome in the maintenance and disruption of immune tolerance with parallels in human studies.
  
  
  CONCLUSIONS
  After years of slow progress, recent research has reduced the translational gap between animal models and clinical therapeutic tolerance. Early detection of autoimmunity, potentially at preclinical stages, offers a window of opportunity for tolerogenic therapy. Reliable biomarkers of tolerance are urgently needed to provide objective measurements of the effectiveness of tolerogenic therapies, and to allow intelligent immunosuppressant withdrawal in patients whose autoimmune disease is stable.
  
  
  BACKGROUND
  See the Video Supplementary Digital Content 1 (http://links.lww.com/COR/A8).
authors.affiliation: The National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, UK.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Baker
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D064591:Allografts; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D015415:Biomarkers / Q000032:analysis; D064987:Cell- and Tissue-Based Therapy; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods* / Q000639:trends; D064307:Microbiota / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D057170:Translational Research, Biomedical; D018183:Transplantation Chimera / Q000276:immunology; D014181:Transplantation Immunology
chemical_list: D015415:Biomarkers