Induction of Transplantation Tolerance via Regulatory T Cells

Authors: Battaglia, Manuela; Grazia Roncarolo, Maria

Source: Inflammation & Allergy - Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy), Volume 5, Number 3, September 2006 , pp. 157-165(9)

Publisher: Bentham Science Publishers

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Abstract:

In the last two decades, graft survival has been greatly improved by the introduction of efficient immunosuppressive drugs. On the other hand, late graft loss caused by chronic rejection together with the side effects of long-term immunosuppression, remain major obstacles for successful transplantation. Operational tolerance, which is defined by the lack of acute and chronic rejection and indefinite graft survival with normal graft function in the absence of chronic immunosuppression, represents an attractive alternative.

Several approaches have been explored to achieve transplantational tolerance, which is considered the “Holy Grail” of transplantation, including induction of central tolerance by establishing mixed chimerism through hematopoietic stem cell transplantation or induction of peripheral tolerance through modulation of allogeneic immune responses. Graft-specific alloreactive T cells, which largely mediate graft rejection, can be silenced through different mechanisms, including deletion, which may occur within the thymus or in the lymphoid organs; anergy, in which alloreactive T cells cannot adequately respond following restimulation with the specific antigen; and suppression, which may be mediated by direct interactions with regulatory T cells (Tregs) or by soluble factors produced by Tregs. This review attempts to summarize the most novel and successful strategies to achieve operational tolerance via induction of Tregs.

Keywords: Transplantation; tolerance; regulatory T cells

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152806778256052

Affiliations: 1: HSR-TIGET Via Olgettina 58, 20132 Milano, Italy.

Publication date: 2006-09-01

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Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

Induction of Transplantation Tolerance via Regulatory T Cells

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