CTLs Get SMAD When Pathogens Tell Them Where to Go

Vaccines protect against infections by eliciting both Ab and T cell responses. Because the immunity wanes as protective epitopes get modified by accruing mutations, developing strategies for immunization against new variants is a major priority for vaccine development. CTLs eliminate cells that support viral replication and provide protection against new variants by targeting epitopes from internal viral proteins. This form of protection has received limited attention during vaccine development, partly because reliable methods for directing pathogen-specific memory CD8 T cells to vulnerable tissues are currently unavailable. In this review we examine how recent studies expand our knowledge of mechanisms that contribute to the functional diversity of CTLs as they respond to infection. We discuss the role of TGF-b and the SMAD signaling cascade during genetic programming of pathogen-specific CTLs and the pathways that promote formation of a newly identified subset of terminally differentiated memory CD8 T cells that localize in the vasculature.