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P16-05. Upregulation of PD-1 and CTLA-4 on HIV-specific T cells in HIV-infected infants
Retrovirology volume 6, Article number: P234 (2009)
Background
Although virus-specific CD8+ T cells have been detected in HIV-infected infants at birth, little is known about their function. Expression of the negative regulatory molecules PD-1 and CTLA-4 on specific T cells in HIV-infected adults is associated with T cell exhaustion and disease progression. We hypothesized that PD-1 and CTLA-4 are also upregulated on specific T cells in HIV-infected infants.
Methods
Twenty HIV+ infants, 25 HIV-exposed uninfected (EU) infants and 25 unexposed uninfected (HIV-) infants from Worcester, South Africa were recruited. Blood was collected at 3, 6, 9 and 12 months of age; none of the infants were on ARV, as the study was completed prior to routine availability in South Africa. Expression of PD-1 and CTLA-4 was measured by flow cytometry on total T cell populations, and on IFN-gamma-producing HIV-specific T cells, following incubation of blood with recombinant vaccinia viruses expressing Gag and Env. Results were analyzed statistically using the non-parametric Mann-Whitney test.
Results
Gag-specific CD4+ T cells and Gag and Env-specific CD8+ T cell responses were detected from as early as 3 months of age in HIV-infected infants. No responses were detected in EU and HIV-infants. PD-1 and CTLA-4 expression on total CD8+ T cells in HIV+ infants was higher than in the EU and HIV-groups, and much more markedly so on HIV-specific IFN-gamma-producing CD4+ and CD8+ T cells.
Conclusion
The immunoregulatory receptors PD-1 and CTLA-4 are upregulated on HIV-specific CD4+ and CD8+ T cells in HIV infected infants not on ARV. Further studies are necessary to determine the relationship between PD-1 and CTLA-4 expression and HIV-specific T cell dysfunction and disease progression in infants.
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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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Nqoko, B., Day, C., Mansoor, N. et al. P16-05. Upregulation of PD-1 and CTLA-4 on HIV-specific T cells in HIV-infected infants. Retrovirology 6 (Suppl 3), P234 (2009). https://doi.org/10.1186/1742-4690-6-S3-P234
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DOI: https://doi.org/10.1186/1742-4690-6-S3-P234
Keywords
- Vaccinia
- Recombinant Vaccinia
- Recombinant Vaccinia Virus
- Infected Infant
- Cell Exhaustion