Regulation of effector and memory T-cell functions by type I interferon

Abstract

Summary Type I interferon (IFN‐α/β) is comprised of a family of highly related molecules that exert potent antiviral activity by interfering with virus replication and spread. IFN‐α/β secretion is tightly regulated through pathogen sensing pathways that are operative in most somatic cells. However, specialized antigen‐presenting plasmacytoid dendritic cells are uniquely equipped with the capacity to secrete extremely high levels of IFN‐α/β, suggesting a key role for this cytokine in priming adaptive T‐cell responses. Recent studies in both mice and humans have demonstrated a role for IFN‐α/β in directly influencing the fate of both CD4+ and CD8+ T cells during the initial phases of antigen recognition. As such, IFN‐α/β, among other innate cytokines, is considered an important ‘third signal’ that shapes the effector and memory T‐cell pool. Moreover, IFN‐α/β also serves as a counter‐regulator of T helper type 2 and type 17 responses, which may be important in the treatment of atopy and autoimmunity, and in the development of novel vaccine adjuvants.

A novel RNA‐based adjuvant combines strong immunostimulatory capacities with a favorable safety profile

“…[33][34][35] Thus, the ability of RNAdjuvant V R to induce high amounts of INF-a in vitro in hPBMCs and in vivo at the injection site in mice underlines its potential as a vaccine adjuvant. In addition to Type I IFN and Type I IFN-stimulated genes (ISGs) the adjuvant induced the upregulation of inflammasome-associated genes 36 such as IL-1b, which is described to be involved in lymphocyte activation and increased IL-12 secretion in dendritic cells.…”

Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

“…In addition, as extrinsic factors, inflammatory signals (signal 3) provided by type I IFN and IL-12 to T cells may be essential modulators in some models (5). Several groups reported that clonal expansion and memory formation by type I IFNR-deficient T cells are reduced during lymphocytic choriomeningitis virus (LCMV) infection but not in vaccinia virus or Listeria monocytogenes infections (6)(7)(8). Furthermore, a number of intrinsic factors control effector cell survival and the development of memory T cells postinfection (9).…”

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

“…Three main types of CpGs have been described: the multimeric CpG-A (or D-type) stimulates plasmacytoid DCs to secrete IFN-α; CpG-B (or K-type) induces B cells and DCs to mature and secrete cytokines such as IL-12p70, IL-6, and TNF-α; and CpG-C has the ability to induce both CpG-A and CpG-B types of responses. In turn, IFN-α secretion from plasmacytoid DCs promotes natural killer T cells (20), CD8 + T-cell activation and cytotoxicity (21), and maturation of conventional DCs. Secretion of IL-12p70 induces Th1 and CTL responses, IL-6 leads to maturation of B cells and induces Th17 responses, and TNF-α stimulates DC maturation and T-cell activation (22)(23)(24).…”