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

1742-4690-6-S3-P240 1742-4690 Poster presentation P16-11. HLA-B57/5801 induces preferential CD27 expression on HIV-Gag but not Nef specific central memory CD8+T cells controlling HIV Xie J Lu W Samri A Costagliola D Schnuriger A da Silva BC Blanc C Almeida M Pellé O Theodorou I Rouzioux C Autran B ALT study group

University Paris VI Pierre et Marie Curie, INSERM UMR-S 945, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France

INSERM U943, Hôpital Pitié-Salpêtrière, UPMC Université Paris 06, Paris, France

Laboratoire de Virologie, Hôpital Necker, Université René Descartes, Paris, France

Retrovirology AIDS Vaccine 2009 Anna Laura Ross Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here. AIDS Vaccine 2009 Paris, France

19–22 October 2009

http://www.hivvaccineenterprise.org/conference/2009/index.aspx 1742-4690 2009 6 Suppl 3 P240 http://www.retrovirology.com/content/6/S3/P240 10.1186/1742-4690-6-S3-P240 22 10 2009 2009 Xie et al; licensee BioMed Central Ltd.

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.