Presented at:
XIX Int'l Congress
Transplantation, Miami, FL, Aug 25-30, 2002
Towards clinical tolerance: Regulatory mechanisms
Kathryn Wood. Oxford, UK
Increasing the immunological specificity of the immunosuppressive therapy that is used to prevent rejection is one of the fundamental objectives for the future development of clinical transplantation.
Novel strategies designed to induce specific immunological unresponsiveness to donor antigens are being introduced into the clinic. These protocols can be grouped into two main categories according to whether the mechanistic objective of the approach is to delete donor antigen reactive cells from the immune repertoire of the recipient and/or to establish and facilitate immunoregulation to control responsiveness to donor antigens after transplantation.
Immunoregulation has the potential to be a powerful mechanism for controlling immune responses to alloantigens. Alloantigen specific regulatory T cells have been identified in recipients with long term surviving grafts. These cells share phenotypic and functional properties with regulatory populations that control responses to self antigens and prevent autoimmune disease.
The successful translation of basic science and preclinical research findings into the clinic remains a major challenge and reliable assays for monitoring the immunological reactivity of the recipient to donor, including the identification of regulatory T cells, are critical for the success of any new approach. The Immune Tolerance Network has been established jointly by the NIH and JDRF to facilitate and support all aspects of this process to make progress towards clinical tolerance a reality.