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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-11. HLA-B57/5801 induces preferential CD27 expression on HIV-Gag but not Nef specific central memory CD8+T cells controlling HIV

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Background

The HLA-B57/5801 allele and characteristics of HIV-specific CD8+T cells play a key role in controlling HIV. To gain novel insight into the nature of the protective effect mediated by HIV-specific CD8+T cells in HLA-B57/5801+ individuals, we compared the frequency, cytokine production, differentiation, and functional avidity of HIV-specific CD8+T cells in B57/5801+ and B57/5801- nonprogressors.

Methods

This study investigated in 53 untreated nonprogressors whether CD8+T cells specific for Gag, Nef and RT differed in their relations to plasma HIV-RNA and cell-associated HIV-DNA loads. Twenty-two patients, 11 HLA-B57/5801+ and 11 B57/5801-, with simultaneous positive responses to Gag and Nef detected by ELISpot assays, were selected for analyzing whether antigen specificity and HLA-restriction trigger CD8+T cell profiles that could explain the association between HLA-B57/5801 and virus control.

Results

The frequency of Gag-specific CD8+T cells negatively correlated with HIV-DNA loads (r = -0.395, p = 0.004), while that of Nef- and RT-specific cells did not. None of these frequencies correlated with plasma HIV-RNA levels. The HIV-Gag and Nef-specific CD8+T cells did not differ for IL-2 production in two HLA groups. In B57/5801+ group, the IFN-γ-producing Gag-specific central memory (CD45RA-CCR7+) CD8+T cells showed a significantly higher proportion of CD27+ cells than their Nef-specific counterparts (p = 0.007). This differentiation pattern was not observed in B57/5801- individuals. These distinct profiles were not explained by the functional avidity against Gag or Nef epitopes. The percentage of CD27 expression on Gag-specific IFN-γ+TCM CD8+T cells negatively correlated with HIV-DNA in the B57/5801+ group (r = -0.683, p = 0.042) but not in the B57/5801- group. The same subset specific for Nef was not correlated with HIV burden whatever the HLA group considered.

Conclusion

Our findings indicate that in HLA-B57/5801+ individuals HIV-Gag induces a preferential CD27+ central-memory differentiation profile distinct from that caused by Nef and that this profile may contribute to the protective effect of Gag-specific CD8+T cells in HLA-B57/5801+ nonprogressors.

Author information

Correspondence to J Xie.

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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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Xie, J., Lu, W., Samri, A. et al. P16-11. HLA-B57/5801 induces preferential CD27 expression on HIV-Gag but not Nef specific central memory CD8+T cells controlling HIV. Retrovirology 6, P240 (2009). https://doi.org/10.1186/1742-4690-6-S3-P240

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Keywords

  • CD27 Expression
  • ELISpot Assay
  • Central Memory
  • Cell Profile
  • Functional Avidity