Generation, homeostasis, and regulation of memory T cells in transplantation

Sensitized individuals experience higher rates of acute rejection and decreased graft survival. Memory T cells have been implicated in these processes, and in the prevention of tolerance induction. A greater understanding of T-cell memory generation, maintenance, and regulation is needed to design new immunosuppressive strategies that prolong graft survival in the presence of alloreactive memory.

Memory T cells are generated against alloantigens via homologous and cross-reactive priming, and recent studies demonstrate that T-cell depletion can also paradoxically result in memory generation. While initially thought to be impervious to regulation due to their enhanced functional properties, memory T cells have shown susceptibility to certain immunomodulating therapies and immunosuppressants and, furthermore, newer targets for memory T-cell regulation show promise in controlling immunological recall.

Current immunosuppression protocols should be designed with consideration of their effects not only on naive T-cell activation, but also on memory generation, activation, and effector function. Additionally, research efforts should continue to identify and manipulate new costimulatory targets and immunosuppressants, which may be key to abrogating memory T-cell responses.