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CD4 regulatory T cells Control CD8 T cell responses to human Herpesvirus 8 lytic and latency proteins


CD8 T cells are considered to play an important role in controlling human herpesvirus 8 (HHV-8/KSHV) infection. However, these T cell responses are non-robust compared to other herpesviruses, suggesting that they are under tight regulatory control.


Longitudinal PBMC samples were obtained from subjects with various outcomes of HHV-8 infection over many years in the Multicenter AIDS Cohort Study. The PBMC were tested by HLA A*0201 multimer staining specific for memory CD8 T cell epitopes of viral lytic and latency proteins, and polyfunctional flow cytometry to detect HHV8-specific, polyfunctional CD8 T cell populations. The effect of Treg was examined by depleting CD4+CD25Hi cells.


Direct staining of PBMC with multimer MHC I complexes showed a relatively high frequency of circulating, HHV-8 lytic and latency antigen-specific CD8 T cells, but low anti-HHV-8 T cell polyfunctional reactivity. Removal of Treg enhanced T cell responses to these HHV-8 epitopes. The frequency of T cells specific for HHV-8 lytic antigens was greater than for latent antigens, and this effect was greater when Treg were removed. Numbers of HHV-8 specific effector memory CD8 T cells increased and terminally differentiated memory CD8 T cells decreased over many years of HHV-8 infection. We are currently assessing anti-HHV-8 T cell and Treg activity in relation to development of KS.


We show for the first time that Treg suppress CD8 T cell responses to HHV-8 lytic and latency antigens, effectively masking more robust, underlying anti-HHV-8 T cell responses. The involvement of CD8 T cells and Treg in control of HHV-8 infection has important implications for development of vaccines to prevent KS.

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Correspondence to Lauren Lepone.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lepone, L., Rappocciolo, G., Piazza, P. et al. CD4 regulatory T cells Control CD8 T cell responses to human Herpesvirus 8 lytic and latency proteins. Infect Agents Cancer 7 (Suppl 1), O17 (2012).

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