The potential of CD4 T-cell memory

While many aspects of memory T-cell immunobiology have been characterized, we suggest that we know only a fraction of the effector functions that CD4 T cells can bring to bear during secondary challenges. Exploring the full impact of memory CD4 T-cell responses is key to the development of improved vaccines against many prominent pathogens, including influenza viruses, and also to a better understanding of the mechanisms of autoimmunity. Here we discuss factors regulating the generation of memory CD4 T cells during the activation of naïve cells and how the nature of the transition from highly activated effector to resting memory upon the resolution of primary responses might impact memory CD4 T-cell heterogeneity in vivo. We stress that memory CD4 T cells have unique functional attributes beyond the secretion of T helper (Th) subset-associated cytokines that can shape highly effective secondary responses through novel mechanisms. These include the recruitment of innate inflammatory responses at early phases of secondary responses as well as the action of enhanced direct effector functions at later phases, in addition to well-established helper roles for CD8 T-cell and B-cell responses.