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. 2012 Aug 20:3:254.
doi: 10.3389/fimmu.2012.00254. eCollection 2012.

Translating tolerogenic therapies to the clinic - where do we stand?

Fadi Issa  1 , Kathryn J Wood
Affiliations

Translating tolerogenic therapies to the clinic - where do we stand?

Fadi Issa et al. Front Immunol. .

Abstract

Manipulation of the immune system to prevent the development of a specific immune response is an ideal strategy to improve outcomes after transplantation. A number of experimental techniques exploiting central and peripheral tolerance mechanisms have demonstrated success, leading to the first early phase clinical trials for tolerance induction. The first major strategy centers on the facilitation of donor-cell mixed chimerism in the transplant recipient with the use of bone marrow or hematopoietic stem cell transplantation. The second strategy, utilizing peripheral regulatory mechanisms, focuses on cellular therapy with regulatory T cells. This review examines the key studies and novel research directions in the field of immunological tolerance.

Keywords: cellular therapy; chimerism; clinical trials; immune regulation; regulatory T cell; tolerance; transplantation.

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Figures

FIGURE 1
FIGURE 1
Development of tolerance through mixed chimerism. A conditioning regimen is administered which consists of a combination of drugs (occasionally together with irradiation) to allow the engraftment of allogeneic bone marrow (BM) or hematopoietic stem cells (HSCs). A bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT) is given the to patient. The donor HSCs seed into the recipient’s BM niches together with the recipient’s HSCs, providing a self-renewing source of donor and recipient hematopoietic cells, leading to widespread multilineage mixed chimerism. Donor dendritic cells seed the thymus, and together with recipient dendritic cells, mediate central clonal deletion of newly developing donor-reactive and recipient-reactive thymocytes. Peripheral regulation also takes place whereby newly developing donor-reactive and recipient-reactive T cells that escape negative selection in the thymus are suppressed in the periphery by regulatory T cells (Treg).
See this image and copyright information in PMC

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