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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-55 LB. The role of CD4+ CD25+ regulatory T cells in the control of IL-10 mediated T cell impairment in chronic HIV Infection

Background

T cell dysfunction in the presence of ongoing antigen exposure is a cardinal feature of chronic viral infections, including HIV. IL-10 has been implicated as an important mediator of this T cell exhaustion. The regulation of IL-10 production, however, remains poorly understood.

Methods

HIV-specific proliferative CD4+ T cell responses were assessed by CFSE assays performed after stimulation with recombinant HIV p24 in the presence of a blocking anti-IL10R antibody or an isotype control, with or without depletion of CD25+ cells. IL-10 production was measured in cell subsets by ICS or by luminex of culture supernatants from PBMCs depleted of CD14+, CD19+ or CD25+ cells. Finally, monocytes and regulatory T cells were sorted and cultured alone or together in transwell plates and secreted IL-10 was measured.

Results

Performing either blockade of IL-10R or depletion of CD25+ cells augmented HIV-specific CD4+ T cell proliferation in viremic patients, but not individuals with controlled viral load. Importantly, depletion of CD25+ cells significantly decreased the responsiveness to IL-10R blockade. ICS showed that CD14+ monocytes were the cellular subset which consistently produced the greatest amount of IL-10. When CD25+ T cells were depleted from PBMCs, however, the amount of IL-10 produced by monocytes was decreased. Consistent with this, purified monocytes that were cultured with regulatory T cells showed increased levels of IL-10 production relative to monocytes cultured alone. Disruption of cell-cell contact between Tregs and monocytes partially abrogated IL-10 induction.

Conclusion

These results indicate that IL-10-mediated inhibition of HIV-specific CD4+ T cell function critically depends on the interplay between regulatory T cells and monocytes. The data demonstrate that monocytes are the primary producers of IL-10 in PBMCs of chronically HIV infected individuals, and regulatory T cells are key inducers of monocyte IL-10 production. This inductive effect appears to be mediated via both diffusible factors and direct cell contact.

Author information

Correspondence to DS Kwon.

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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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Kwon, D., Angin, M., Streeck, H. et al. P16-55 LB. The role of CD4+ CD25+ regulatory T cells in the control of IL-10 mediated T cell impairment in chronic HIV Infection. Retrovirology 6, P408 (2009). https://doi.org/10.1186/1742-4690-6-S3-P408

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Keywords

  • Chronic Viral Infection
  • Transwell Plate
  • Cell Exhaustion
  • Cellular Subset
  • Direct Cell Contact