Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid.
Vgamma9/Vdelta2 (gammadelta) T cells play a major role in innate immunity against microbes, stressed, and tumor cells. They represent less than 5% of peripheral blood lymphocytes but can be activated and expanded in vitro by aminobisphosphonates (ABP)-treated monocytes. The aim of this work was to determine whether ABP-treated dendritic cells (DCs) can also activate gammadelta T cells and regulate immune responses mediated by conventional alphabeta T cells. Highly purified immature (iDC) and mature DC (mDC) were generated from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol-treated iDC and mDC retained their immunostimulatory properties and induced the vigorous expansion of central memory and effector memory gammadelta T cells. gammadelta T cells displayed antitumor activity and appropriate cell surface antigens to target secondary lymphoid organs and exert costimulatory activity. Antigen-specific MHC-restricted immune responses, mediated by conventional alphabeta T cells, were improved by the concurrent gammadelta T-cell activation. In conclusion, large numbers of gammadelta T cells with effector and costimulatory activities are rapidly generated by Zol-treated iDC/mDC. This strategy is worthy of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.
Fiore
Francesca
F
Division of Hematology, University of Turin, Via Genova 3, 10126 Turin, Italy.
Castella
Barbara
B
Nuschak
Barbara
B
Bertieri
Raffaello
R
Mariani
Sara
S
Bruno
Benedetto
B
Pantaleoni
Francesca
F
Foglietta
Myriam
M
Boccadoro
Mario
M
Massaia
Massimo
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004164:Diphosphonates / Q000494:pharmacology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D007156:Immunologic Memory / Q000187:drug effects; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D000077211:Zoledronic Acid
D000276:Adjuvants, Immunologic; D050071:Bone Density Conservation Agents; D019496:Cancer Vaccines; D004164:Diphosphonates; D006649:Histocompatibility Antigens; D007093:Imidazoles; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid