Reshaping the past: Strategies for modulating T-cell memory immune responses

Memory T cells are generated following an initial encounter with antigen, persist over the lifetime of an individual, and mediate rapid and robust functional responses upon antigenic recall. While immune memory is generally associated with protective immune response to pathogens, memory T cells can be generated to diverse types of antigens including autoantigens and alloantigens through homologous or crossreactive priming and comprise the majority of circulating T cells during adulthood. Memory T cells can therefore play critical roles in propagating and perpetuating autoimmune disease and in mediating allograft rejection, although the precise pathways for regulation of memory immune responses remain largely undefined. Moreover, evaluating and designing strategies to modulate memory T-cell responses are challenging given the remarkable heterogeneity of memory T cells, with different subsets predominating in lymphoid versus non-lymphoid tissue sites. In this review, we discuss what is presently known regarding the effect of current immunomodulation strategies on the memory T-cell compartment and potential strategies for controlling immunological recall.