Activated V gamma 9V delta 2 T cells trigger granulocyte functions via MCP-2 release.
Vgamma9Vdelta2 T cells display a broad antimicrobial activity by directly killing infected cells and by inducing an effective adaptive immune response. The activation of Vgamma9Vdelta2 T cells by aminobisphosphonate drugs such as zoledronic acid (ZOL) results in a massive release of cytokines and chemokines that may induce a bystander activation of other immune cells. The aim of this work was to evaluate the ability of soluble factors released by ZOL-activated Vgamma9Vdelta2 T cells to induce granulocyte activation. We showed that soluble factors released by ZOL-stimulated Vgamma9Vdelta2 T cells activate granulocytes by inducing their chemotaxis, phagocytosis, and alpha-defensins release. Proteomic analysis allowed us to identify a number of cytokines and chemokines specifically released by activated Vgamma9Vdelta2 T cells. Moreover, MCP-2 depletion by neutralizing Ab revealed a critical role of this chemokine in induction of granulocyte alpha-defensins release. Altogether, these data show a Vgamma9Vdelta2-mediated activation of granulocytes through a bystander mechanism, and confirm the wide ability of Vgamma9Vdelta2 T-lymphocytes in orchestrating the immune response. In conclusion, an immune modulating strategy targeting Vgamma9Vdelta2 T cells may represent a key switch to induce an effective and well-coordinated immune response, and can be proposed as a way to strengthen the immune competence during infectious diseases.
Agrati
Chiara
C
National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. agrati@inmi.it
Cimini
Eleonora
E
Sacchi
Alessandra
A
Bordoni
Veronica
V
Gioia
Cristiana
C
Casetti
Rita
R
Turchi
Federica
F
Tripodi
Marco
M
Martini
Federico
F
D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054412:Chemokine CCL8 / Q000378:metabolism* / Q000502:physiology; D018920:Coculture Techniques; D004164:Diphosphonates / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000077211:Zoledronic Acid; D023084:alpha-Defensins / Q000378:metabolism
C515453:CCL8 protein, human; D054412:Chemokine CCL8; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023084:alpha-Defensins; D000077211:Zoledronic Acid