title: Zoledronic acid and interleukin-2 treatment improves immunocompetence in HIV-infected persons by activating Vgamma9Vdelta2 T cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Cellular Immunology, National Institute for Infectious Diseases, LazzaroSpallanzani I.R.C.C.S., Rome 00149, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Poccia
authors.forename: Cristiana
authors.initials: C
authors.lastname: Gioia
authors.forename: Federico
authors.initials: F
authors.lastname: Martini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sacchi
authors.forename: Paola
authors.initials: P
authors.lastname: Piacentini
authors.forename: Massimo
authors.initials: M
authors.lastname: Tempestilli
authors.forename: Chiara
authors.initials: C
authors.lastname: Agrati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Amendola
authors.forename: Amina
authors.initials: A
authors.lastname: Abdeddaim
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Vlassi
authors.forename: Miroslav
authors.initials: M
authors.lastname: Malkovsky
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007121:Immunocompetence / Q000187:drug effects; D007156:Immunologic Memory; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D000077211:Zoledronic Acid
chemical_list: D000276:Adjuvants, Immunologic; D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D000077211:Zoledronic Acid