OBJECTIVE: gammadelta T cells bearing the Vgamma9Vdelta2 T-cell receptor exert many antiviral effector functions in humans, including release of anti-HIV factors and direct cytotoxicity against virus-infected cells. Moreover, they are known to activate dendritic cells, improving antigen presentation function. After HIV infection, Vgamma9Vdelta2 T-cell number and reactivity are rapidly affected and they decrease upon disease progression. Bisphosphonate drugs such as zoledronic acid (Zol), used to treat bone diseases, have been shown to induce in vivo, in combination with interleukin-2, Vgamma9Vdelta2 T-cells' activation. The aim of this work was to verify whether the administration of Zol in combination with interleukin-2 in HIV-infected patients might improve Vgamma9Vdelta2 T-cell function, including immune adjuvancy mediated by gammadelta-dendritic cell cross-talk. DESIGN AND METHODS: In HIV patients naive to antiretroviral therapy, we analyzed the effect of combined Zol and interleukin-2 treatment, in comparison to Zol alone, on Vgamma9Vdelta2 T-cell number, maturation and function, on dendritic cell activation and on HIV-specific CD8 T-cell response. RESULTS: Zol and interleukin-2-combined treatment induced in-vivo Vgamma9Vdelta2 T-cell expansion and maturation. Paralleling Vgamma9Vdelta2 T-cell activation, increased dendritic cell maturation and HIV-specific CD8 T-cell responses were found. CONCLUSION: The specific modulation of Vgamma9Vdelta2 T-cell number and responsiveness after HIV infection may be at least transiently restored in vivo by Zol and interleukin-2 treatment. In this way, the immune effector mechanisms, secondary to Vgamma9Vdelta2 T-cell activation, were improved, suggesting a possible adjuvancy role of Zol and interleukin-2 treatment in restoring innate and specific competence in HIV-infected persons.
OBJECTIVE: gammadelta T cells bearing the Vgamma9Vdelta2 T-cell receptor exert many antiviral effector functions in humans, including release of anti-HIV factors and direct cytotoxicity against virus-infected cells. Moreover, they are known to activate dendritic cells, improving antigen presentation function. After HIV infection, Vgamma9Vdelta2 T-cell number and reactivity are rapidly affected and they decrease upon disease progression. Bisphosphonate drugs such as zoledronic acid (Zol), used to treat bone diseases, have been shown to induce in vivo, in combination with interleukin-2, Vgamma9Vdelta2 T-cells' activation. The aim of this work was to verify whether the administration of Zol in combination with interleukin-2 in HIV-infectedpatients might improve Vgamma9Vdelta2 T-cell function, including immune adjuvancy mediated by gammadelta-dendritic cell cross-talk. DESIGN AND METHODS: In HIV patients naive to antiretroviral therapy, we analyzed the effect of combined Zol and interleukin-2 treatment, in comparison to Zol alone, on Vgamma9Vdelta2 T-cell number, maturation and function, on dendritic cell activation and on HIV-specific CD8 T-cell response. RESULTS:Zol and interleukin-2-combined treatment induced in-vivo Vgamma9Vdelta2 T-cell expansion and maturation. Paralleling Vgamma9Vdelta2 T-cell activation, increased dendritic cell maturation and HIV-specific CD8 T-cell responses were found. CONCLUSION: The specific modulation of Vgamma9Vdelta2 T-cell number and responsiveness after HIV infection may be at least transiently restored in vivo by Zol and interleukin-2 treatment. In this way, the immune effector mechanisms, secondary to Vgamma9Vdelta2 T-cell activation, were improved, suggesting a possible adjuvancy role of Zol and interleukin-2 treatment in restoring innate and specific competence in HIV-infectedpersons.
Authors: Carolina Garrido; Matthew L Clohosey; Chloe P Whitworth; Michael Hudgens; David M Margolis; Natalia Soriano-Sarabia Journal: JCI Insight Date: 2018-06-21