PMID- 15990565
OWN - NLM
STAT- MEDLINE
DCOM- 20060209
LR  - 20190718
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 19
IP  - 11
DP  - 2005 Jul 22
TI  - Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is 
      regulated by CXCR4-gp120 interactions.
PG  - 1125-33
AB  - BACKGROUND: Sensitivity towards apoptosis induced by ligation of the tumor 
      necrosis factor family of death receptors is controlled in part by death receptor 
      expression. Whereas cellular activation enhances Fas receptor expression and 
      induces Fas sensitivity, such cellular activation neither alters TRAIL receptor 
      expression nor induces TRAIL sensitivity. Cells infected by HIV acquire 
      sensitivity to TRAIL induced death, although the mechanisms by which this is 
      achieved are undefined. OBJECTIVE: To define the mechanism by which cells from 
      HIV infected patients acquire sensitivity to TRAIL mediated killing. DESIGN: In 
      vitro assessment of TRAIL receptor expression and TRAIL sensitivity. METHODS: 
      Treatment of Jurkat T cells, peripheral blood lymphocytes from HIV negative 
      donors, or human osteogenic seroma (HOS) cells expressing CD4, CXCR4 or CCR5 with 
      T tropic gp120, M tropic gp120, or agonistic antibodies against CD4, CXCR4 or 
      CCR5. TRAIL receptors were measured by flow cytometry or reverse 
      transcription-PCR and TRAIL sensitivity was assessed by incubation with 
      recombinant TRAIL followed by Annexin V fluorescein isothiocyanate/Propidium 
      Iodide (PI) staining. RESULTS: Treatment of uninfected Jurkat T cells, as well as 
      primary T cells with gp120 results in the upregulation of TRAIL death receptor 
      expression and acquired sensitivity to TRAIL mediated cell death. The increase in 
      TRAIL death receptor expression and acquisition of TRAIL sensitivity requires the 
      chemokine coreceptor CXCR4 but not CCR5 or the CD4 receptor. CONCLUSIONS: These 
      results indicate that chemokine receptor interactions regulate TRAIL receptor 
      expression and provide an explanation for the acquired T cell sensitivity to 
      TRAIL mediated killing death during HIV infection.
FAU - Lum, Julian J
AU  - Lum JJ
AD  - Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
FAU - Schnepple, David J
AU  - Schnepple DJ
FAU - Badley, Andrew D
AU  - Badley AD
LA  - eng
GR  - R01 AI062261-01/AI/NIAID NIH HHS/United States
GR  - R01 AI40384/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Apoptosis/physiology
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - CD4-Positive T-Lymphocytes/*metabolism/pathology
MH  - HIV Envelope Protein gp120/*metabolism
MH  - HIV Infections/*metabolism/pathology
MH  - Humans
MH  - Jurkat Cells
MH  - Membrane Glycoproteins/*metabolism
MH  - Receptors, CCR5/metabolism
MH  - Receptors, CXCR4/*metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Up-Regulation
EDAT- 2005/07/02 09:00
MHDA- 2006/02/10 09:00
CRDT- 2005/07/02 09:00
PHST- 2005/07/02 09:00 [pubmed]
PHST- 2006/02/10 09:00 [medline]
PHST- 2005/07/02 09:00 [entrez]
AID - 00002030-200507220-00006 [pii]
AID - 10.1097/01.aids.0000176212.16205.23 [doi]
PST - ppublish
SO  - AIDS. 2005 Jul 22;19(11):1125-33. doi: 10.1097/01.aids.0000176212.16205.23.