Molecular pathways regulating CD4+ T cell differentiation, anergy and memory with implications for vaccines

CD4+ T cells occupy a central role in the induction and regulation of adaptive immune responses. Activated CD4+ T helper (Th) cells exert immediate effector functions by producing cytokines and chemokines, providing help for the induction of CD8+ cytotoxic T lymphocyte responses and memory, and providing help for immunoglobulin class switching, affinity maturation of antibody and B cell memory. Inherent in naïve CD4+ T cells is the flexibility to adopt alternate lineage potentials, which depend upon regulatory mechanisms that change with tissue microenvironment and upon infection. Here, we discuss lineage instructive programs that regulate CD4+ T cell differentiation and memory and how to translate this knowledge into vaccines and immunotherapies that promote protective immune responses.