{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nguyen TP"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","Case Western Reserve University","National Institutes of Health"],"pagination":["1139-46"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4438745"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["97(6)"],"pubmed_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-induced P-Akt as a potential mechanism to disrupt homeostasis of T lymphocytes."],"journal":["Journal of leukocyte biology"],"pubmed_title":["Interferon-α inhibits CD4 T cell responses to interleukin-7 and interleukin-2 and selectively interferes with Akt signaling."],"pmcid":["PMC4438745"],"funding_grant_id":["AI-036219","AI-104480","R21 AI104480","P30 AI036219","P01 AI055793","R01 AI069085","R01 AI034343","T32 AI089474"],"pubmed_authors":["Mudd JC","Harding CV","Sieg SF","Bazdar DA","Nguyen TP","Lederman MM","Hardy GA"],"additional_accession":[]},"is_claimable":false,"name":"Interferon-α inhibits CD4 T cell responses to interleukin-7 and interleukin-2 and selectively interferes with Akt signaling.","description":"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-induced P-Akt as a potential mechanism to disrupt homeostasis of T lymphocytes.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jun","modification":"2024-11-21T08:58:39.112Z","creation":"2019-03-27T01:51:55Z"},"accession":"S-EPMC4438745","cross_references":{"pubmed":["25784743"],"doi":["10.1189/jlb.4A0714-345RR","10.1189/jlb.4a0714-345rr"]}}