Overcoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among...

This review highlights recent advances in our understanding of the frequency and nature of alloreactivity among memory T-cell populations, and discusses recent successes in experimentally targeting these populations in order to prolong graft survival.

Recent studies suggest that not only is alloreactivity present within peripheral T-cell compartments of normal healthy individuals, but cross-reactivity between viral-specific T cells and allotropes may in fact be a very common occurrence. Furthermore, this cross-reactivity functions at the level of molecular mimicry of T-cell receptor recognition. Therapeutics that specifically target cell surface molecules or effector pathways used by memory T cells to mediate graft rejection will likely be required in order to attenuate the donor-reactive memory T-cell response during transplantation.

A major challenge facing the field over the next decade is to define the heterogeneity that exists within memory T-cell populations that impacts graft survival. Understanding the functional and phenotypic differences that modify the memory T-cell barrier to tolerance induction might allow a strategy in which strength of immunosuppression could be tailored to fit the immunological history of a given transplant recipient in order to minimize nonimmune toxicities, maximize protective immunity, and prolong graft survival.