title: HIV immune activation drives increased Eomes expression in memory CD8 T cells in association with transcriptional downregulation of CD127.
abstract: BACKGROUND
  During HIV infection distinct mechanisms drive immune activation of the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8 T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific T cells. One consequence of this immune activation is a profound decrease in IL-7Rα (CD127) expression on memory CD8 T cells. The mechanisms leading to this are unknown and because of the potential impact of reduced IL-7 signaling in memory T cells specific to HIV and other pathogens, in the present study we examined the molecular mechanisms implicated in this downregulation of CD127.
  
  
  METHODS
  Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in healthy controls and HIV-infected patients were studied by flow cytometry.
  
  
  RESULTS
  CD127 downregulation occurs at the transcriptional level for both mIL7RA and sIL7RA alternative spliced forms in the CD127 memory CD8 T cells. CD127 memory CD8 T cells exhibited increased Eomes expression and an 'effector-like' gene profile. These changes were associated with higher HIV-RNA levels. Following combination antiretroviral therapy (cART), there was an increase in CD127 expression over an extended period of time (>5 months) which was associated with decreased Eomes expression.
  
  
  CONCLUSIONS
  CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression.
authors: aCMRS/Laboratory of Immunoregulation, NIAID bExperimental Immunology Branch, NCI, NIH, Bethesda cLaboratory of Molecular Immunoregulation, NCI, NIH, Frederick dBiostatistics Research Branch, NIAID, NIH, Bethesda eCollaborative Clinical Research Branch, NIAID, NIH, Frederick, Maryland, USA.
authors: Rebecca B
authors: RB
authors: Hasley
authors: Changwan
authors: C
authors: Hong
authors: Wenqing
authors: W
authors: Li
authors: Travis
authors: T
authors: Friesen
authors: Yoriko
authors: Y
authors: Nakamura
authors: Grace Y
authors: GY
authors: Kim
authors: Jung-Hyun
authors: JH
authors: Park
authors: Julie A
authors: JA
authors: Hixon
authors: Scott
authors: S
authors: Durum
authors: Zonghui
authors: Z
authors: Hu
authors: Michael C
authors: MC
authors: Sneller
authors: Raphael
authors: R
authors: Oguariri
authors: Tomozumi
authors: T
authors: Imamichi
authors: H Clifford
authors: HC
authors: Lane
authors: Marta
authors: M
authors: Catalfamo
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000096:biosynthesis*
chemical_list: C491199:EOMES protein, human; D053699:Interleukin-7 Receptor alpha Subunit; D020825:T-Box Domain Proteins
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