title: 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.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  IL-7 responsiveness is impaired in immune failure patients and may be related to expression of CD127 and IFN-α.
authors.affiliation: aDepartment of Medicine, Division of Infectious Diseases and HIV Medicine bDepartment of Pathology, Case Western Reserve University/University Hospitals Case Medical Center cCenter for AIDS Research, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Thao P
authors.initials: TP
authors.lastname: Nguyen
authors.forename: Supriya
authors.initials: S
authors.lastname: Shukla
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000074243:Immune Reconstitution; D016898:Interferon-alpha / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: C508605:IL7 protein, human; D016898:Interferon-alpha; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit