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Responsiveness to IL-7 but not to IFN-α is diminished in CD4+ T cells from treated HIV infected patients who experience poor CD4+ T-cell recovery.

Responsiveness to IL-7 but not to IFN-α is diminished in CD4+ T cells from treated HIV infected patients who experience poor CD4+ T-cell recovery.
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Nguyen TP, Shukla S, Asaad R, Freeman ML, Lederman MM, Harding CV, Sieg SF,


Nguyen TP, Shukla S, Asaad R, Freeman ML, Lederman MM, Harding CV, Sieg SF, (click to view)

Nguyen TP, Shukla S, Asaad R, Freeman ML, Lederman MM, Harding CV, Sieg SF,

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AIDS (London, England) 30(13) 2033-42 doi 10.1097/QAD.0000000000001161

Abstract
OBJECTIVE
To assess CD4 T-cell responsiveness to IL-7 and IFN-α in HIV-infected patients who experience poor recovery of CD4 T-cell counts during therapy (immune failure patients).

DESIGN
Responses to IL-7 and IFN-α were compared between HIV-infected immune failure (CD4 cell counts <379 cells/μl) patients and immune success (CD4 cell counts >500 cells/μl) as well as healthy control patients.

METHODS
Flow cytometry was used to assess peripheral blood mononuclear cells for IL-7-induced proliferation, CD25 expression, and signaling (signal transducer and activator of transcription 5 phosphorylation and Akt phosphorylation) in CD4 T cells. Freshly isolated cells were characterized by expression of IL-7Rα (CD127) among CD4 T-cell maturation subsets by flow cytometry and sorted CD3 T cells were assessed for expression of IFN-α and interferon stimulated genes (2′-5′-oligoadenylate synthetase-1 and myxovirus resistance A protein) by quantitative real-time PCR. Responses to IFN-α were assessed by induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of IL-7-induced CD4 T-cell proliferation.

RESULTS
IL-7-induced proliferation and CD25 expression were decreased in CD4 T cells from immune failure patients. CD127 expressing CD4 T cells were decreased, whereas expression of 2′-5′-oligoadenylate synthetase-1, myxovirus resistance A protein, and IFN-α mRNA were increased in total CD3 T cells from immune failure patients. CD127 expression correlated with CD25 induction but not proliferation, whereas T-cell IFN-α mRNA was associated with reduced proliferation in CD4 T cells from immune failure patients. IFN-α-mediated induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of proliferation were not diminished in CD4 T cells from immune failure patients.

CONCLUSION
IL-7 responsiveness is impaired in immune failure patients and may be related to expression of CD127 and IFN-α.

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