Harnessing FOXP3+ regulatory T cells for transplantation tolerance
Herman Waldmann, Robert Hilbrands, Duncan Howie, Stephen Cobbold
Herman Waldmann, Robert Hilbrands, Duncan Howie, Stephen Cobbold
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Review

Harnessing FOXP3+ regulatory T cells for transplantation tolerance

Abstract

Early demonstrations that mice could be tolerized to transplanted tissues with short courses of immunosuppressive therapy and that with regard to tolerance to self, CD4+FOXP3+ regulatory T cells (Tregs) appeared to play a critical role, have catalyzed strategies to harness FOXP3-dependent processes to control rejection in human transplantation. This review seeks to examine the scientific underpinning for this new approach to finesse immunosuppression.

Authors

Herman Waldmann, Robert Hilbrands, Duncan Howie, Stephen Cobbold

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Figure 2

In the absence of clinically available non–T cell–depleting coreceptor and costimulator blockade, T cell depletion may be exploited as an alternative approach to achieve operational tolerance.

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In the absence of clinically available non–T cell–depleting coreceptor a...
Lymphocyte depletion is typically followed by homeostatic proliferation, resulting in a rebound of effector T (Teff) and memory T (Tmem) cells (upper panel). This process is driven by cytokines such as IL-7 and is not matched by an adequate repopulation of Tregs, thereby impeding the mechanisms required for induction of operational tolerance. If, however, the reconstitution phase can be guided to favor early emergence of Tregs, then operational tolerance might be possible (lower panel). Recent advances in understanding the molecular and epigenetic mechanisms of FOXP3 expression and Treg differentiation will enable such new associated treatments (Rx) that selectively favor Treg reconstitution. These “favored” Tregs will, among other activities, orchestrate the development of immune privilege at the tissue site.