Heterogeneity within T cell memory: Implications for transplant tolerance

Abstract

Adaptive immunity in both mouse and man results in the generation of immunological memory. Memory T cells are both friend and foe to transplant recipients, as they are intimately involved and in many cases absolutely required for the maintenance of protec- tive immunity in the face immunosuppression, yet from the evidence presented herein they clearly constitute a formidable barrier for the successful implementation of tolerance induction strategies in transplantation. This review describes the experimental evidence demonstrating the increased resistance of memory T cells to many distinct tolerance induction strategies, and outlines recent advances in our knowledge of the ways in which alloreactive memory T cells arise in previously untransplanted individuals. Understanding the impact of alloreactive memory T cell specificity, frequency, and quality might allow for better donor selection in order to minimize the donor-reactive memory T cell barrier in an individual transplant recipient, thus allowing stratification of relative risk of alloreactive memory T cell mediated rejection, and conversely increase the likelihood of successful establishment of tolerance. However, further research into the molecular and cellular path- ways involved in alloreactive memoryT cell-mediated rejection is required in order to design new strategies to overcome the memoryT cell barrier, without critically impairing protective immunity. © 2012 Krummey and Ford.