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

Abstract

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.

Figure 1

Type I interferon (IFN) regulates CD4⁺ T helper cell development. IFN-α/β contributes to various functions of T helper type 1 (Th1) cells, particularly the secretion of interleukin-2 (IL-2) by memory cells. Conversely, IFN-α/β restricts the development of alternative populations such as Th2 and Th17. pDCs, plasmacytoid dendritic cells; TLR, toll-like receptor.

Figure 2

Interferon-α/β (IFN-α/β) supports CD8⁺ T-cell priming through direct effects on both the antigen-presenting cells and the T cells. IFN-α/β signalling in antigen-presenting cells enhances their ability to activate CD8⁺ T cells. IFN-α/β also acts directly on CD8⁺ T cells to support the development of effector and memory populations. DC, dendritic cell; IL-2, interleukin-2; TLR, toll-like receptor.