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The Journal of Immunology, 2007, 179: 3057-3064.
Copyright © 2007 by The American Association of Immunologists, Inc.

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Central Memory V{gamma}9V{delta}2 T Lymphocytes Primed and Expanded by Bacillus Calmette-Guérin-Infected Dendritic Cells Kill Mycobacterial-Infected Monocytes1

Angelo Martino2, Rita Casetti, Alessandra Sacchi and Fabrizio Poccia3

Unit of Cellular Immunology, "Fabrizio Poccia," National Institute for Infectious Diseases "Lazzaro Spallanzani," Instituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy

In humans, innate immune recognition of mycobacteria, including Mycobacterium tuberculosis and bacillus Calmette-Guérin (BCG), is a feature of cells as dendritic cells (DC) and {gamma}{delta} T cells. In this study, we show that BCG infection of human monocyte-derived DC induces a rapid activation of V{gamma}9V{delta}2 T cells (the major subset of {gamma}{delta} T cell pool in human peripheral blood). Indeed, in the presence of BCG-infected DC, V{gamma}9V{delta}2 T cells increase both their expression of CD69 and CD25 and the production of TNF-{alpha} and IFN-{gamma}, in contrast to DC treated with V{gamma}9V{delta}2 T cell-specific Ags. Without further exogenous stimuli, BCG-infected DC expand a functionally cytotoxic central memory V{gamma}9V{delta}2 T cell population. This subset does not display lymph node homing receptors, but express a high amount of perforin. They are highly efficient in the killing of mycobacterial-infected primary monocytes or human monocytic THP-1 cells preserving the viability of cocultured, infected DC. This study provides further evidences about the complex relationship between important players of innate immunity and suggests an immunoregulatory role of V{gamma}9V{delta}2 T cells in the control of mycobacterial infection.

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, Ricerca Corrente and Finalizzata (04.126) and by the TB-VAC FP6 European Project.

2 Address correspondence and reprint requests to Dr. Angelo Martino, Unit of Cellular Immunology, National Institute for Infectious Diseases, "Lazzaro Spallanzani," Instituto di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, Rome, Italy. E-mail address: martino{at}inmi.it

3 This article is dedicated to Fabrizio Poccia, who died June 12, 2007. The Unit of Cellular Immunology has been renamed in his memory.

4 Abbreviations used in this paper: IPP, isopentenyl-pyrosphosphate; Zol, Zoledronic acid; DC, dendritic cell; BCG, bacillus Calmette-Guérin; imDC, immature DC; LDH, lactate dehydrogenase; CM, central memory.







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