Zoledronic acid and interleukin-2 treatment improves immunocompetence in HIV-infected persons by activating Vγ9Vδ2 T cells

Objective: gamma delta T cells bearing the V gamma 9V delta 2 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, V gamma 9V delta w 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, V gamma 9V delta 2 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 V gamma 9V delta 2 T-cell function, including immune adjuvancy mediated by gamma delta-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 V gamma 9V delta 2 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 V gamma 9V delta 2 T-cell expansion and maturation. Paralleling V gamma 9V delta 2 T-cell activation, increased dendritic cell maturation and HIV-specific CD8 T-cell responses were found. Conclusion: The specific modulation of V gamma 9V delta 2 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 V gamma 9V delta 2 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. (c) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins