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Volume 6 Supplement 3

AIDS Vaccine 2009

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

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 homeostasis and activation, rather than a direct consequence of virus-replication. Therefore, we compared T-cell homeostatsis 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) compared 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 resting 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 declining 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 production or sequestration to non-blood compartments may also contribute.

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Correspondence to KC Groves.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Groves, K., Bibby, D., Isaksen, A. et al. P16-21. Altered T cell homeostasis and activation in HIV-1 elite suppressors with low CD4+ T-cell counts. Retrovirology 6, P250 (2009). https://doi.org/10.1186/1742-4690-6-S3-P250

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Keywords

  • Uninfected Control
  • Cell Homeostasis
  • Uninfected Individual
  • Rare Subset
  • Viral Influence