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

Fabrizio Poccia, Cristiana Gioia, Federico Martini, Alessandra Sacchi, Paola Piacentini, Massimo Tempestilli, Chiara Agrati, Alessandra Amendola, Amina Abdeddaim, Chrysoula Vlassi, Miroslav Malkovsky, Gianpiero D'Offizi

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: γδ T cells bearing the Vγ9Vδ2 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, Vγ9Vδ2 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, Vγ9Vδ2 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 Vγ9Vδ2 T-cell function, including immune adjuvancy mediated by 78-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 Vγ9Vδ2 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 Vγ9Vδ2 T-cell expansion and maturation. Paralleling Vγ9Vδ2 T-cell activation, increased dendritic cell maturation and HIV-specific CD8 T-cell responses were found. Conclusion: The specific modulation of Vγ9Vδ2 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 Vγ9Vδ2 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.

Original languageEnglish
Pages (from-to)555-565
Number of pages11
JournalAIDS (London, England)
Volume23
Issue number5
DOIs
Publication statusPublished - Mar 13 2009

Keywords

  • Adjuvancy
  • Bis-phosphonates
  • HIV-specific response
  • Immunomodulating drugs
  • Innate immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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