Review Article | Published:

Regulation of antiviral T cell responses by type I interferons

Nature Reviews Immunology volume 15, pages 231242 (2015) | Download Citation

Abstract

Type I interferons (IFNs) are pro-inflammatory cytokines that are rapidly induced in different cell types during viral infections. The consequences of type I IFN signalling include direct antiviral activity, innate immune cell activation and regulation of adaptive immune responses. In this Review, we discuss recent conceptual advances in our understanding of indirect and direct regulation of T cell immunity by type I IFNs, which can either promote or inhibit T cell activation, proliferation, differentiation and survival. This regulation depends, to a large extent, on the timing of type I IFN exposure relative to T cell receptor signalling. Type I IFNs also provide activated T cells with resistance to natural killer cell-mediated elimination.

Key points

  • Type I interferons (IFNs) are pro-inflammatory cytokines that have an essential role during viral infections.

  • Type I IFNs not only function as innate cytokines but are also involved in regulating antiviral T cell responses.

  • Regulation of antiviral T cells by type I IFNs occurs through both direct signalling on T cells and indirect signalling through accessory cells.

  • Indirect regulation of T cells by type I IFNs is mediated by both the innate antiviral functions of type I IFNs, and by the modulation of antigen-presenting cell function.

  • Direct signalling of type I IFNs on T cells can have both augmenting and inhibitory effects, contingent on the timing of the signal relative to T cell receptor activation.

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Acknowledgements

The authors are grateful to the members of the Oxenius group for helpful discussions and critical reading of the manuscript. This work was supported by the Swiss Federal Institute of Technology (ETH) and the Swiss National Science Foundation (grant numbers 310030-113947 and 310030_146140 to A.O.) by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony, Germany (to U.K.), and by the SFB 854 (TP B15 to U.K.) of the German Research Council.

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Affiliations

  1. Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland.

    • Josh Crouse
    •  & Annette Oxenius
  2. Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany.

    • Ulrich Kalinke

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Annette Oxenius.

Glossary

Plasmacytoid dendritic cells

(pDCs). A subset of DCs that are described as plasmacytoid because their microscopic appearance resembles that of plasmablasts. On a per-cell basis, pDCs are important producers of type I interferons in response to viral infections or Toll-like receptor stimulation.

Signal 3 cytokine

During T cell activation, T cell receptor signals (signal 1) and co-stimulatory signals (signal 2) initiate proliferation of naive T cells; however, they also require a specific cytokine signal (known as signal 3) to differentiate into effector and memory T cells. The most prominent signal 3 cytokines for CD8+ T cell activation are interleukin-12 and type I interferons.

Metallophilic macrophages

A population of macrophages found in the spleen that is located around the white pulp adjacent to the marginal sinus. These cells express constitutive levels of Ubl carboxy-terminal hydrolase 18 (USP18), a negative regulator of type I interferon signalling, and are thus more vulnerable to infection with type I interferon-sensitive viruses than other myeloid cells.

Superantigen

A microbial protein that activates all of the T cells expressing a particular set of T cell receptor (TCR) Vβ chains by crosslinking the TCR to a particular MHC molecule, regardless of the peptide presented.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nri3806

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