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2015 ; 6
(ä): 242
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Differential sensitivity of regulatory and effector T cells to cell death: a
prerequisite for transplant tolerance
#MMPMID26042125
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Front Immunol
2015[]; 6
(ä): 242
PMID26042125
show ga
Despite significant progress achieved in transplantation, immunosuppressive
therapies currently used to prevent graft rejection are still endowed with severe
side effects impairing their efficiency over the long term. Thus, the development
of graft-specific, non-toxic innovative therapeutic strategies has become a major
challenge, the goal being to selectively target alloreactive effector T cells
while sparing CD4(+)Foxp3(+) regulatory T cells (Tregs) to promote operational
tolerance. Various approaches, notably the one based on monoclonal antibodies or
fusion proteins directed against the TCR/CD3 complex, TCR coreceptors, or
costimulatory molecules, have been proposed to reduce the alloreactive T cell
pool, which is an essential prerequisite to create a therapeutic window allowing
Tregs to induce and maintain allograft tolerance. In this mini review, we focus
on the differential sensitivity of Tregs and effector T cells to the depleting
and inhibitory effect of these immunotherapies, with a particular emphasis on
CD3-specific antibodies that beyond their immunosuppressive effect, also express
potent tolerogenic capacities.