The relationship between the extrinsic environment and the internal transcriptional network is circular . Naive T cells first engage with antigen-presenting cells to set transcriptional differentiation networks in motion . In turn, this regulates specific chemokine receptors that direct migration into distinct lymph node niches . Movement into these regions brings newly activated T cells into contact with accessory cells and cytokines that reinforce the differentiation programming to specify T cell function . We and others have observed similarities in the transcriptional networks that specify both CD4+ T follicular helper (T FH) cells and CD8+ central memory stem-like (T SCM) cells . Here, we compare and contrast the current knowledge for these shared differentiation programs, compared to their effector counterparts, CD4+ T-helper 1 (T H1) and CD8+ short-lived effector (T SLEC) cells . Understanding the interplay between cellular interactions and transcriptional programming is essential to harness T cell differentiation that is fit for purpose; to stimulate potent T cell effector function for the elimination of chronic infection and cancer; or to amplify the formation of humoral immunity and longevity of cellular memory to prevent infectious diseases.
Index: T cell differentiation, T follicular helper, cellular interactions, lymphoid niche, migration, stem-like memory, transcriptional regulation