P. A. J. Haslett*, S. W. Zhu, W. Hanekom, and G.Kaplan.
The Rockefeller Univ., New York, NY.
Background:The CD8 T cell response has the potential to contribute to the control of HIV replication in infected individuals. It is therefore important to identify new therapeutic methods of enhancing antiviral CD8 T cell immunity. Thalidomide is an immune modulatory drug that we have shown to costimulate T cells. We hypothesize that this activity of thalidomide boosts the responses of CD8 T cells that are engaging specific antigen.
Methods:Using cells from patients chronically co-infected with HIV and CMV, we performed in vitro experiments to study the effect of thalidomide on virus-specific CD8 T cell function. We set up cocultures of freshly isolated CD8 T cells with autologous monocyte-derived dendritic cells that had been infected with recombinant vaccinia viruses (VV) expressing HIV (gag, pol or env) or CMV (pp65) genes or with wild-type VV (control) in the presence or absence of thalidomide. On day 7, T cells were restimulated and their responses were detected by cytofluorometric analysis of intracellular interferon-g(IFN-g) and TNF-α;and by IFN-gELISPOT.
Results:We observed that (1) HIV-specific CD8 T cells generally produced IFN-gbut not TNF-α;, while CMV- specific CD8 T cells produced both cytokines; (2) thalidomide consistently augmented the number of virus-specific, cytokine-secreting CD8 T cells in a dose-dependent manner but did not alter the pre-existing patterns of cytokine secretion observed in response to HIV and CMV; )3) preliminarily, we observed that thalidomide treatment of two patients for 21 days induced increased numbers of circulating CMV- and HIV-specific T cells in vivo.
Conclusion:Thalidomide has the potential, unique for an orally administered drug, to boost pre-existing antiviral immunity and may have a therapeutic role in chronic HIV and CMV infection.© 8th Conference on Retroviruses and Opportunistic Infections