Challenges in the pursuit of immune tolerance

• Published in: Immunological reviews Vol. 241; no. 1; pp. 49 - 62
• Main Authors: Nepom, Gerald T., St. Clair, E. William, Turka, Laurence A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Blackwell
• Subjects: Allergic diseases; allergy; Analytical, structural and metabolic biochemistry; Animals; Antibodies, Monoclonal - therapeutic use; Autoimmune diseases; autoimmunity; Biological and medical sciences; biomarkers; Chimerism; Clinical trials; Clinical Trials as Topic; Desensitization, Immunologic; Effector cells; Fundamental and applied biological sciences. Psychology; Graft rejection; Hemopoiesis; Humans; Immune System Diseases - immunology; Immune System Diseases - therapy; Immune Tolerance; immune-mediated disease; Immunity; Immunological tolerance; Immunomodulation; Immunoregulation; immunosuppression; Immunotherapy - trends; Inflammation; Lymphocyte Depletion; T-Lymphocytes, Regulatory - immunology; Therapeutic applications; tolerance; transplantation; Autoimmunity; Immunopathology; Allergy; Immunosuppression; Treatment; Surgery; Immune tolerance; Graft; Biochemistry; Transplantation; immune-mediated disease; tolerance
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/j.1600-065X.2011.01003.x

Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune‐mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovative therapeutic intervention to restore stability. The Immune Tolerance Network, an international consortium sponsored by the National Institutes of Health, seeks to advance both the scientific understanding and the clinical success of immune therapies for these disorders, through an innovative and collaborative effort involving clinical trials and mechanistic studies. Over the last decade, scientists have evaluated cell‐based ablation and deviation strategies in trials using lymphocyte‐specific targeting, induction of host‐donor hematopoietic chimerism, induction of antigen‐specific immune regulation, and a variety of antigen desensitization approaches. In this article, we review some of the highlights of this experience and discuss the potential for progress, utilizing new insights into regulatory mechanisms and biomarker signatures of tolerance.