Abstract
Interleukin (IL)-10 is an important regulatory cytokine that can modulate excessive immune mediated injury. Several distinct cell types have been demonstrated to produce IL-10, including most recently CD8+ cytotoxic T lymphocytes (CTLs) responding to respiratory virus infection. Here we report that CD4+ T cell help in the form of IL-2 is required for IL-10 production by CTLs, but not for the induction of CTL effector cytokines. We show that IL-2 derived from CD4+ helper T cells cooperates with innate immune cell–derived IL-27 to amplify IL-10 production by CTLs through a Blimp-1-dependent mechanism. These findings reveal a previously unrecognized pathway that coordinates signals derived from innate and helper T cells to control the production of a regulatory cytokine by CTLs during acute viral infection.
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Acknowledgements
We thank the rest of Braciale laboratory for critical comments and B. Small for excellent technical assistance. We thank C.L. Karp (Cincinnati Children's Hospital Medical Center), M. Mohrs (Trudeau Institute), W. Leonard (US National Institutes of Health) and T.R. Malek (University of Miami) for reagents. This work was supported by the US National Institutes of Health (grants AI-15608, HL-33391, AI-37293 and U19 AI-083024 to T.J.B.), University of Virginia Center for Immunity, Inflammation and Regenerative Medicine start-up funds to R.S. and an American Lung Association Postdoctoral Fellowship (RN-123000) to J.S.
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J.S. designed the project, performed most of the experimental work, analyzed the data and wrote the manuscript. H.D. and E.K.M. performed some of the quantitative RT-PCR and ELISA experiments. R.S. contributed to reagents and suggestions. T.J.B. supervised the project, analyzed the data and wrote the manuscript.
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Sun, J., Dodd, H., Moser, E. et al. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol 12, 327–334 (2011). https://doi.org/10.1038/ni.1996
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DOI: https://doi.org/10.1038/ni.1996
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