T-cell quality in memory and protection: implications for vaccine design

Effector and memory CD4+ T helper 1 (TH1) and CD8+ T cells exhibit remarkable phenotypic and functional heterogeneity. The heterogeneity of such responses has important implications for whether they are protective or not.Development of techniques to more fully characterize T-cell responses will lead to a better fundamental understanding of T-cell effector and memory differentiation as well as function. Multiparameter flow cytometry is a technique that has been used to simultaneously evaluate the secretion of multiple cytokines by a single T cell.The ability to delineate a number of discrete functional populations of CD4+ TH1 and CD8+ T cells based on their pattern of cytokine secretion is termed the quality of the response. The demonstration that TH1 and CD8+ T cells that produce multiple cytokines have enhanced effector function and correlate best with protection establishes that the quality of the response is a crucial aspect of T-cell biology.The factors that control the quality of the response include antigen dose and innate immunity.Vaccine design for infections requiring T cells to mediate protection can now be tailored to optimize both the magnitude and quality of T cells that provide durable immunity and protection.