Heterogeneous memory T cells in antiviral immunity and immunopathology

Memory T cells are generated following an initial viral infection, and have the potential for mediating robust protective immunity to viral re-challenge due to their rapid and enhanced functional responses. In recent years, it has become clear that the memory T cell response to most viruses is remarkably diverse in phenotype, function, and tissue distribution, and can undergo dynamic changes during its long-term maintenance in vivo. However, the role of this variegation and compartmentalizationof memory T cells in protective immunity to viruses remains unclear. In this review,we discuss the diverse features of memory T cells that can delineate different subsets, the characteristics of memory T cells thus far identified to promote protective immune responses, and how the heterogeneous nature of memory T cells may also promote immunopathology during antiviral responses. We propose that given the profound heterogeneity of memory T cells, regulation of memory T cells during secondary responses could focus the response to participation of specific subsets,and/or inhibit memory T-cell subsets and functions that can lead to immunopathology.