Zoledronic acid and interleukin-2 treatment improves immunocompetence in HIV-infected persons by activating Vgamma9Vdelta2 T cells.
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.
Poccia
Fabrizio
F
Laboratory of Cellular Immunology, National Institute for Infectious Diseases, LazzaroSpallanzani I.R.C.C.S., Rome 00149, Italy.
Gioia
Cristiana
C
Martini
Federico
F
Sacchi
Alessandra
A
Piacentini
Paola
P
Tempestilli
Massimo
M
Agrati
Chiara
C
Amendola
Alessandra
A
Abdeddaim
Amina
A
Vlassi
Chrysoula
C
Malkovsky
Miroslav
M
D'Offizi
Gianpiero
G
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
D000276:Adjuvants, Immunologic; D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D000077211:Zoledronic Acid