Chronic exposure to type-I IFN under lymphopenic conditions alters CD4 T cell homeostasis
Cecile Le Saout, Rebecca B Hasley, Hiromi Imamichi, Lueng Tcheung, Zonghui Hu, Megan A Luckey, Jung-Hyun Park, Scott K Durum, Mindy Smith, Adam W Rupert, Michael C Sneller, H Clifford Lane, Marta Catalfamo, Cecile Le Saout, Rebecca B Hasley, Hiromi Imamichi, Lueng Tcheung, Zonghui Hu, Megan A Luckey, Jung-Hyun Park, Scott K Durum, Mindy Smith, Adam W Rupert, Michael C Sneller, H Clifford Lane, Marta Catalfamo
Abstract
HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-α on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-α. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis.
Conflict of interest statement
AWR is affiliated with AIDS Monitoring Labs, Leidos Biomedical Research, Inc. This does not alter our adherence to all PLOS Pathogens policies on sharing data and materials.
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References
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