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Vaccines work by eliciting an immune response and consequent immunological memory that mediates protection from infection or disease. Recently, new methods have been developed to dissect the immune response in experimental animals and humans, which have led to increased understanding of the molecular mechanisms that control differentiation and maintenance of memory T and B cells. In this review we will provide an overview of the cellular organization of immune memory and underline some of the outstanding questions on immunological memory and how they pertain to vaccination strategies. Finally we will discuss how we can learn about antigen design from the interrogation of our memory T and B cells—a journey from vaccines to memory and back. [ABSTRACT FROM AUTHOR]

Discusses how dendritic cells (DC) provide a quantitative and qualitative framework for T cell antigen recognition. Requirements for activation and differentiation of naive T cells; Mechanism by which DC assembles the components into discrete packets; Determination of magnitude and class of T cell responses.

Dendritic cells are professional antigen-presenting cells that mediate immunity and tolerance. uncover a new route for dendritic cell production in vivo. They show that in response to infection by gram-negative bacteria, monocytes are recruited to the lymph node where they rapidly differentiate into dendritic cells that present antigens to T cells. [Copyright &y& Elsevier]

Summary: T follicular helper (Tfh) cells provide help to B cells and are crucial for establishment of germinal center (GC) reactions, including production of high-affinity antibodies and generation of memory B cells and long-lived plasma cells. Here we report that the magnitude of the Tfh cell response was dictated by the amount of antigen and directly correlated with the magnitude of the GC B cell response. In addition, maintenance of the Tfh cell phenotype required sustained antigenic stimulation by GC B cells. In lymphopenic conditions, a strong and prolonged Tfh cell response led to bystander B cell activation, hypergammaglobulinemia, and production of poly- and self-reactive antibodies. These data demonstrate that antigen dose determines the size and duration of the Tfh cell response and GC reaction, highlight the transient nature of the Tfh cell phenotype, and suggest a link between overstimulation of Tfh cells and the development of dysregulated humoral immune responses. [Copyright &y& Elsevier]

Summary Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses. [ABSTRACT FROM AUTHOR]