Anderson, SA

Boasso, A

Dolan, MJ

Fuchs, D

Hardy, AW

Herbeuval, JP

Lifson, JD

Shearer, GM

English

PubMed

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BioMed Central
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Retrovirology
Open AccessPoster presentation
HIV activates indoleamine 2,3-dioxygenease: inhibition of T cell 
proliferation by tryptophan starvation
A Boasso*1, AW Hardy1, JP Herbeuval1, SA Anderson2, MJ Dolan2, JD Lifson3, 
D Fuchs4 and GM Shearer1
Address: 1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA, 2Henry M. 
Jackson Foundation and Infectious Diseases Service Wilford Hall Medical Center, Lackland Air Force Base, Texas, USA, 3Division of Biological 
Chemistry, Innsbruck Medical University, Innsbruck, Austria and 4AIDS Vaccine Program, SAIC, National Cancer Institute, Frederick, Maryland, 
USA
* Corresponding author    
T cell immune responses of HIV+ patients are functionally
impaired prior to CD4+ T cell depletion. Tryptophan (trp)
degradation by indoleamine-2, 3-dyoxigenase (IDO) is an
immunosuppressive system that may be important in
HIV/AIDS. We show here that IDO is increased in PBMC
from HIV+ patients compared to controls. Culture with
the IDO-inhibitor 1-methyl tryptophan (1 mT) increased
proliferation of PBMC from HIV+ patients in response to
PHA or anti-CD3/CD28. Exposure of PBMC from HIV-
uninfected donors to infectious or noninfectious HIV
increased IDO in plasmacytoid dendritic cells (pDC).
Supernatants from HIV-exposed PBMC inhibited CD4+ T
cell responses to PHA or anti-CD3/CD28, and this effect
was reversed by 1 mT. CD8+ T cell proliferation in
response to anti-CD3/CD28, but not to PHA, was also
inhibited. Analysis of cyclin mRNA expression showed
that CD4+ T cell were arrested in G1, whereas CD8+ T cell
were blocked in G0. HIV-induced IDO inhibited expres-
sion of CD28 mRNA in CD8+ T cells. Thus HIV directly
induces IDO expression in pDC, resulting in unrespon-
siveness of CD4+ T cells by inhibiting progression to the S
phase of the cell cycle, and blocking of CD8+ T cell cos-
timulation through downregulation of CD28.
from 2006 International Meeting of The Institute of Human Virology
Baltimore, USA. 17–21 November, 2006
Published: 21 December 2006
Retrovirology 2006, 3(Suppl 1):P11 doi:10.1186/1742-4690-3-S1-P11
<supplement> <title> <p>2006 International Meeting of The Institute of Human Virology</p> </title> <note>Meeting abstracts. A single PDF containing all abstracts in this Supplement is available <a href=" http://www.biomedcentral.com/content/files/pdf/1742-4690-3-S1-full.pdf ">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-3-S1-info.pdf</url></supplement>
© 2006 Boasso et al; licensee BioMed Central Ltd. 


HIV activates indoleamine 2,3-dioxygenease: inhibition of T cell proliferation by tryptophan starvation

A Boasso

AW Hardy

JP Herbeuval

SA Anderson

MJ Dolan

JD Lifson

D Fuchs

GM Shearer

file:///data/core-remote/dit/data/Springer-OA/pdf/de0/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc0Mi00NjkwLTMtUzEtUDExLnBkZg==.pdf

HIV activates indoleamine 2,3-dioxygenease: inhibition of T cell proliferation by tryptophan starvation

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