Interferon-α inhibits CD4 T cell responses to interleukin-7 and interleukin-2 and selectively interferes with Akt signaling

Journal of Leukocyte Biology
Thao P NguyenScott F Sieg

Abstract

Persistent type I IFN production occurs during chronic viral infections, such as HIV disease. As type I IFNs have antiproliferative activity, it is possible that chronic exposure to these cytokines could adversely affect T cell homeostasis. We investigated the capacity of IFN-α to impair T cell proliferation induced by the homeostatic cytokine, IL-7, or another common γ-chain cytokine, IL-2, in cells from healthy human donors. We found that IL-7- or IL-2-induced proliferation of CD4(+) T cells was partially inhibited in the presence of IFN-α. The CD4(+) T cells that were exposed to IFN-α also displayed attenuated induction of IL-2 and CD40L following TCR stimulation. Analyses of signaling pathways indicated that IL-7 and IL-2 induced a delayed and sustained P-Akt signal that lasted for several days and was partially inhibited by IFN-α. In contrast, IL-7-induced P-STAT5 was not affected by IFN-α. Furthermore, IFN-α had no detectable effect on P-Akt that was induced by the chemokine SDF-1. Both inhibitors of P-Akt and P-STAT5 blocked IL-7-induced T cell proliferation, confirming that both signaling pathways are important for IL-7-induced T cell proliferation. These results demonstrate that IFN-α can selectively inhibit cytokine-i...Continue Reading

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Citations

Sep 25, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Michael L FreemanMichael M Lederman
May 11, 2016·Journal of Neurotrauma·Ali DarkazalliCathy W Levenson
Jun 21, 2016·The Journal of Clinical Investigation·Souheil-Antoine YounesMichael M Lederman
Dec 5, 2017·JCI Insight·Cecile Le SaoutMarta Catalfamo
Jul 1, 2016·Journal of Virology·Xavier Dagenais-LussierJulien van Grevenynghe
Dec 3, 2015·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Carey L ShiveMichael M Lederman
Oct 29, 2019·PLoS Pathogens·Xavier Dagenais-LussierUNKNOWN Montreal Primary Infection Study Group
Jan 6, 2016·Current Opinion in HIV and AIDS·Netanya S Utay, Peter W Hunt

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