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Cutting Edge: T-bet and IL-27R Are Critical for In Vivo IFN- Production by CD8 T Cells during Infection¹

Trudeau Institute, Saranac Lake, NY 12983

CD8⁺ T cells are a major source of IFN-, a key effector cytokine in immune responses against many viruses and protozoa. Although the transcription factor T-bet is required for IFN- expression in CD4⁺ T cells, it is reportedly dispensable in CD8⁺ T cells, where the transcription factor Eomesodermin is thought to be sufficient. The diverse functions of IFN- are mediated through the IFN-R and STAT1. In CD4⁺ T cells, STAT1 appears to be critical for the activation of T-bet and IFN-, suggesting an IFN--dependent positive feedback loop. However, STAT1 can also be activated by other cytokines, including IL-27. In the present study we show that, in contrast to in vitro conditions and the prevailing paradigm, T-bet is critical for the in vivo IFN- production by CD8⁺ T cells upon infection of mice with diverse pathogens. Whereas IFN-R signals are dispensable for the T-bet-dependent IFN- production, direct IL-27R signals are critical.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funds from Trudeau Institute and by National Institutes of Health Grants AI46530 and AI067723 (to A.M.C.), AI61587 (to L.L.J.), AI067967 and AI49823 (to D.L.W.), and AI046530 (to M.M.).

² Current address: National Institute of Allergy and Infectious Diseases, 50 South Drive, National Institutes of Health, Bethesda, MD 20892-8003.

³ Address correspondence and reprint requests to Dr. Markus Mohrs, Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, E-mail address: mmohrs{at}trudeauinstitute.org

⁴ Abbreviations used in this paper: BM, bone marrow; FluNP, MHC class I peptide tetramer specific for the influenza virus nucleoprotein NP_366–374/D^b; WT, wild type; YFP, yellow fluorescent protein.

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