NIAID Plan for Research on Immune Tolerance

Part 1: Overview

As the leading NIH Institute for research in immunology, the NIAID is in a unique position to capitalize on advances in basic, pre-clinical and clinical research focused on achieving immune tolerance for immune-mediated diseases, including autoimmune and allergic diseases as well as transplant rejection. This research plan provides a broad-based set of strategies and initiatives to further our understanding of immune tolerance and to accelerate the clinical evaluation of tolerogenic approaches to treat and prevent immune system diseases.

Overall Conceptual Framework

The plan provides an effective model for translational research and for ensuring that key studies are performed in a coordinated and efficient manner. The plan is designed around a mechanism-based (as opposed to a disease-oriented) approach, focusing on immune tolerance as the overall scientific framework and clinical objective. The goal is to begin a more collaborative and coordinated research effort-one involving basic immunologists, relevant clinical specialties, other NIH Institutes and the pharmaceutical and biotechnology industry. Major features of the plan are outlined below.

• Establish new, and use existing, clinical research infrastructures to accelerate multi-center studies, including cooperative clinical trial groups in kidney transplantation, islet transplantation, autoimmune and allergic diseases.

• Incorporate studies of underlying mechanisms in non-human primate and clinical research.

• Incorporate developmental work to identify and validate surrogate markers of immune tolerance as well as disease stage, activity and therapeutic response.

• Engage the participation of the pharmaceutical and biotechnology industry by creating an infrastructure that will accelerate quality pre-clinical and clinical research.

• Support basic research to expand knowledge of the molecular basis for tolerance induction and maintenance and innovative research to expand the universe of tolerogenic approaches.

• Ensure the availability of critical research resources, including research training programs for physicians and Ph.D.s.

Major Scientific Approaches to Immune Tolerance

• Co-stimulatory blockade (e.g., anti-CD40 ligand, anti-B7, CTLA4-Ig)

• Cytokine modulation (e.g., IL-4, IL-12, TNF, TGFß

• Deletion of responding lymphocytes (e.g., Fas-ligand)

• Other approaches, such as leukocyte migration blockade, peptide-based therapies targeted at specific antigens, and the use of molecularly engineered cells and tissues for deletion or inactivation of pathogenic lymphocytes.

Key Components of the Research Plan

• Transplantation

  • Kidney transplantation

  • Islet transplantation

• Autoimmune Diseases

  • Type 1 Diabetes Mellitus

  • Multiple Sclerosis

  • Rheumatoid Arthritis

  • Systemic Lupus Erythematosus

• Asthma and Allergic Diseases

• Cross-Cutting Research

  • Human Immunology Cooperative Study Groups

  • Research Resources

  • Exploratory/Developmental Research

  • Basic Studies for Future Discovery

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