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9V
2 T Cells Trigger Granulocyte Functions via MCP-2 Release1,2National Institute for Infectious Diseases "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
V
9V
2 T cells display a broad antimicrobial activity by directly killing infected cells and by inducing an effective adaptive immune response. The activation of V
9V
2 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 V
9V
2 T cells to induce granulocyte activation. We showed that soluble factors released by ZOL-stimulated V
9V
2 T cells activate granulocytes by inducing their chemotaxis, phagocytosis, and
-defensins release. Proteomic analysis allowed us to identify a number of cytokines and chemokines specifically released by activated V
9V
2 T cells. Moreover, MCP-2 depletion by neutralizing Ab revealed a critical role of this chemokine in induction of granulocyte
-defensins release. Altogether, these data show a V
9V
2-mediated activation of granulocytes through a bystander mechanism, and confirm the wide ability of V
9V
2 T-lymphocytes in orchestrating the immune response. In conclusion, an immune modulating strategy targeting V
9V
2 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Italian Ministry of Health and from the Evaluation of Longterm non progressor Viro-immunological Italian Studies Concerted Action (ISS AIDS 40G.66).
2 This work is in memory of Fabrizio Poccia, boss, teacher, and friend, who enjoyed making science too briefly.
3 Address correspondence and reprint requests to Dr. Chiara Agrati, Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani" I.R.C.C.S., Padiglione Del Vecchio, Via Portuense 292, Rome, Italy. E-mail address: agrati{at}inmi.it
4 Abbreviations used in this paper: IPP, isopentenyl pyrophosphate; ZOL, zoledronic acid; SF, soluble factor; SF-
, SFs obtained from 
cultures; SF-Mon, SFs obtained from monocytes cultures; SF-
/Mon, SFs obtained from 
/Monocytes cocultures.
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