Harnessing regulatory T cells for transplant tolerance in the clinic through mTOR inhibition: myth or reality?

    loading  Checking for direct PDF access through Ovid


Purpose of reviewThe inhibition of mTOR promotes immune tolerance in mouse models of transplantation, by favoring the expansion of regulatory T cells over effector T cells. However, attempts at inducing immune tolerance with the mTOR inhibitor (mTOR-I) in humans have so far failed. We herein review the immunological obstacles that need to be overcome in order to translate mTOR-I-related tolerogenic properties into the clinic.Recent findingsOur knowledge of regulatory T-cell biology has exploded over the past few years, providing clues to explain the complex impact of prolonged mTOR inhibition on the biology of regulatory T cells. Furthermore, recent data have shed light on the unexpected pro-inflammatory burst observed in some transplant recipients treated with mTOR-I. We propose that the exposure of an organism to pathogens determines the immunodominant effect of mTOR-I, altering the immune system from a state of tolerance in inbred animals to a state of infection-triggered enhanced inflammation in humans.SummaryRecent advances in the understanding of the pleiotropic effects of mTOR-I on the immune system are paving the way to new therapeutic avenues. Future mTOR-I-based tolerogenic protocols should counter the mTOR-I-related inflammation in order to selectively promote expansion of stable regulatory T cells. We herein envisage promising therapeutic perspectives.

    loading  Loading Related Articles