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Developing new vaccination strategies and optimizing current vaccines through heterologous prime-boost carries the promise of integrating the benefits of different yet synergistic vectors. It has been widely thought that the increased immunity afforded by heterologous prime-boost vaccination is mainly due to the minimization of immune responses to the carrier vectors, which allows a progressive build up of immunity against defined epitopes and the subsequent induction of broader immune responses against pathogens. Focusing on CD8+ T cells, we put forward a different yet complementary hypothesis based primarily on the systematic analysis of DNA vaccines as priming agents. This hypothesis relies on the finding that during the initiation of immune response, acquisition of co-inhibitory receptors such as programmed cell death-1 (PD-1) is determined by the pattern of antigen exposure in conjunction with Toll-like receptor (TLR)-dependent stimulation, critically affecting the magnitude and profile of secondary immunity. This hypothesis, based upon the acquisition and co-regulation of pivotal inhibitory receptors by CD8+ T cells, offers a rationale for gene-based immunization as an effective priming strategy and, in addition, outlines a new dimension to immune homeostasis during immune reaction to pathogens. Finally, this model implies that new and optimized immunization approaches for cancer and certain viral infections must induce highly efficacious T cells, refractory to a broad range of immune-inhibiting mechanisms, rather than solely or primarily focusing on the generation of large pools of vaccine-specific lymphocytes. [ABSTRACT FROM AUTHOR]

The immune system evolved to rapidly recognize infectious threats and promptly mobilize cellular effectors to the infection site. Establishment of a robust T1-type immunity is a prerequisite for effective defense against most viruses and intracellular bacteria. However, accumulating evidence shows that T1 and T2 responses during such infections are not mutually exclusive. A possibility may be that the dual T1–T2 nature of antiviral immune responses is merely a byproduct of less than perfect crossregulatory mechanisms. Herein, we discuss molecular and cellular mechanisms of T-cell differentiation along with recent evidence supporting the hypothesis that rather than representing an epiphenomenon, coinduction of virus-specific T2 cells plays a significant homeostatic role. Thus, molecular pathways that regulate IL-4 production during influenza virus infection monitor T1-mediated immune responses in vital organs such as lungs and prevent immune pathology that may otherwise interfere with recovery from disease. Such evidence suggests that coinduction of T2 immunity maintains immune homeostasis during T1-mediated defense reactions. Finally, we outline implications on the earlier concept of T1/T2 dichotomy, supporting a model in which these two subsets, rather than being mutually antagonistic, together facilitate the recovery from infection. [ABSTRACT FROM AUTHOR]

The article discusses several papers published within the issue including one about the immune suppressing role of major histocompatibility complex (MHC), another regarding polyclonal immunoglobulin therapy and a paper on immune danger sensing through the unfolded protein response (UPR)

The article introduces various topics covered in the issue including immunity and its role in infectious and non-infectious diseases, perturbation of host homeostasis due to infection or other tissue damage, and the role of miRNA in the regulation of various aspects of innate immunity.

The article discusses various papers published within the issue including one on the immune recognition pathways that monitor RNA, one on tolerogenic dendritic cells (DC), and another on the immune dysfunction related to chronic dialysis.

Abstract: DNA vaccines or peptides are capable of inducing specific immunity; however, their translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein, we demonstrate that a novel immunization strategy, encompassing sequential exposure of the lymph node milieu to plasmid and peptide in a heterologous prime-boost fashion, results in considerable MHC class I-restricted immunity in mice. Plasmid-primed antigen expression was essential for the generation of a population of central memory T cells, expressing CD62L and low in PD-1, with substantial capability to expand and differentiate to peripheral memory and effector cells, following subsequent exposure to peptide. These vaccine-induced T cells dominated the T cell repertoire, were able to produce large amounts of chemokines and pro-inflammatory cytokines, and recognized tumor cells effectively. In addition to outlining a feasible and effective method to transform plasmid DNA vaccination into a potentially viable immunotherapeutic approach for cancer, this study sheds light on the mechanism of heterologous prime-boost and the considerable heterogeneity of MHC class I-restricted T cell responses. [Copyright &y& Elsevier]

Presents a study which provided evidence of the role of motifs associated with noncoding RNA in the immune response reminiscent of viral infection, mediating rapid induction of proinflammatory chemokine expression, recruitment and activation of antigen-presenting cells and others. Methods; Results; Discussion.