Anderson, J

Bibby, D

Deayton, J

Groves, KC

Isaksen, A

McKnight, Á

Orkin, C

Stagg, AJ

Retrovirology

English

PubMed

KC Groves

D Bibby

A Isaksen

J Deayton

J Anderson

C Orkin

AJ Stagg

Á McKnight

Springer - Publisher Connector

P16-21. Altered T cell homeostasis and activation in HIV-1 elite suppressors with low CD4+ T-cell counts

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BioMed Central
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Retrovirology
Open AccessPoster presentation
P16-21. Altered T cell homeostasis and activation in HIV-1 elite 
suppressors with low CD4+ T-cell counts
KC Groves*1, D Bibby2, A Isaksen2, J Deayton3, J Anderson4, C Orkin2, 
AJ Stagg3 and Á McKnight3
Address: 1Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK, 2Barts and the London 
NHS Trust, London, UK, 3ICMS, Barts and The London School of Medicine and Dentistry, London, UK and 4Homerton University Hospital NHS 
Foundation Trust, London, UK
* Corresponding author    
Background
HIV-1 elite-suppressors (ES) maintain low viral-load (VL)
without therapy and classically maintain normal
CD4+counts. We have identified a rare subset with falling
CD4+counts (discord-ES). Disease progression in these
patients may result from a viral influence on T-cell home-
ostasis and activation, rather than a direct consequence of
virus-replication. Therefore, we compared T-cell homeo-
statsis and activation in discord-ES and typical-ES.
Methods
Fresh whole blood samples were obtained from 8 discord-
ES (VL<2000 copies/ml >1 year, CD4+count <450 × 106/
L), 12 typical-ES (VL<2000 copies/ml >1 year, CD4+count
>450 × 106/L), 5 progressors (VL>5000 copies/ml,
CD4+count <450 × 106/L) and 5 uninfected individuals.
Using multiparameter flow-cytometry we quantified
naïve and memory T-cell subsets based on expression of
CD45RA/RO and CD62L, and assessed activation based
on co-expression of CD38 and HLA-DR.
Results
Blood from discord-ES contained fewer naïve
(CD45RA+62L+) CD4+ T-cells than blood from typical-ES
(median 80[IQR 52–121] versus 277[218–401]; p =
0.001). This lower number of naive T-cells represented a
lower proportion of total CD4+ T-cells. Numbers of naive
CD4+ T-cells in discord-ES did not differ significantly from
those in progressors and were reduced (p = 0.002) com-
pared with uninfected controls. A similar pattern was
observed with regard to numbers of CD4+ central-memory
(CD45RO+CD62L+) and effector-memory
(CD45RO+CD62L-) populations. Both activated and rest-
ing naive CD4+ T-cells were reduced in number in discord-
ES, but activated cells constituted an increased proportion
of the naive CD4+ pool compared with typical-ES (p =
0.003).
Conclusion
CD4+ T-cell subsets and their activation in discord-ES are
distinct from those in typical-ES and indistinguishable
from those in progressors, suggesting that CD4+ T-cell
decline is more closely associated with perturbations in T-
cell activation than with VL. The increased proportion of
activated naïve CD4+ T-cells against a backdrop of declin-
ing numbers of these cells in discord-ES may suggest that
activation contributes to progressive cell-loss despite only
low-level viral-replication. However, impaired T-cell pro-
duction or sequestration to non-blood compartments
may also contribute.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P250 doi:10.1186/1742-4690-6-S3-P250
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P250
© 2009 Groves et al; licensee BioMed Central Ltd. 


https://retrovirology.biomedcentral.com/track/pdf/10.1186/1742-4690-6-S3-P250?site=retrovirology.biomedcentral.com

P16-21. Altered T cell homeostasis and activation in HIV-1 elite suppressors with low CD4+ T-cell counts

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