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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-10. IL-2 therapy mediates expansion of Treg cells, maintains IL-17 expressing CD4+ T-cells and selectively suppresses HIV specific T-cell responses

Background

Preservation of IL-17 producing CD4 + T (Th17) cell populations may be beneficial in HIV-1 disease. Despite broad interest in the role of Th17 cells in regulating human immune responses little is known about the manipulation of IL-17 in humans in vivo. IL-2 has been used in conjunction with antiretrovirals to increase CD4+ T-cell counts in HIV-1, and is approved in some European countries for this purpose. We sought to gauge the effects of IL-2 administration on IL-17 production and inflammatory T cell responses among recently HIV infected persons who had achieved virologic suppression on an anti-retroviral regimen.

Methods

We randomized persons to receive or not receive a course of IL-2 over 1 year and measured by flow cytometry T cell responses to polyclonal and viral peptide specific stimulation, T regulatory populations (T-reg, CD3+CD4+CD25+/CD127-FoxP3+) T cell activation (CD38/HLA-DR) and changes in maturation profiles of T cells (CD27, CD28, CD45RA).

Results

Those who received IL-2 showed a significantly greater expansion of CD4+ T cells and T-regs compared with participants who did not receive IL-2. Counts of Th17 cells did not change in response to IL-2 administration. The degree of expansion in T-regs was significantly associated with the degree of drop in inflammatory T cell responses, a relationship which was independent of T cell activation. We observed that administration of IL-2 mediated: an expansion of T-regs, that was not associated with a change in Th17 cells; expanded naive CD4+ T cells; and a selective decline in HIV-1 Gag-specific T cell IFN-γ responses in participants that received IL-2.

Conclusion

Our data suggests IL-2 limits production of but does not reverse Th17 cells in humans and to achieve a state of increased CD4+ T cell IL-17 expression additional immune based in vivo interventions will need to be evaluated.

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Correspondence to L Ndhlovu.

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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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Ndhlovu, L., Sinclair, E., Epling, L. et al. P16-10. IL-2 therapy mediates expansion of Treg cells, maintains IL-17 expressing CD4+ T-cells and selectively suppresses HIV specific T-cell responses. Retrovirology 6, P239 (2009). https://doi.org/10.1186/1742-4690-6-S3-P239

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Keywords

  • Th17 Cell
  • Treg Cell
  • Virologic Suppression
  • Viral Peptide
  • Maturation Profile