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The Journal of Immunology, 2001, 166: 7190-7199.
Copyright © 2001 by The American Association of Immunologists

Production of TNF-{alpha} by Human V{gamma}9V{delta}2 T Cells Via Engagement of Fc{gamma}RIIIA, the Low Affinity Type 3 Receptor for the Fc Portion of IgG, Expressed upon TCR Activation by Nonpeptidic Antigen1

Virginie Lafont2, Janny Liautard, Jean Pierre Liautard and Jean Favero

Institut National de la Santé et de la Recherche Médicale, Unité 431, Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier II, Montpellier, France

Human lymphocytes expressing the {gamma}{delta} TCR represent a minor T cell subpopulation found in blood. The majority of these cells express V{gamma}9V{delta}2 determinants and respond to nonpeptidic phosphoantigens. Several studies have shown that, in vivo, the percentage of V{gamma}9V{delta}2 T cells dramatically increases during pathological infection, leading to the hypothesis that they play an important role in the defense against pathogens. However, the specific mechanisms involved in this response remain poorly understood. It has been established that V{gamma}9V{delta}2 T cells display potent cytotoxic activity against virus-infected and tumor cells, thereby resembling NK cells. In this study, we show that, upon stimulation by nonpeptidic Ags, V{gamma}9V{delta}2 T cells express Fc{gamma}RIIIA (CD16), a receptor that is constitutively expressed on NK cells. CD16 appears to be an activation Ag for V{gamma}9V{delta}2 T cells. Indeed, ligation of CD16 on V{gamma}9V{delta}2 T cells leads to TNF-{alpha} production. This TNF-{alpha} production, which is dependent (like that induced via the TCR-CD3 complex) on the activation of the p38 and extracellular signal-regulated kinase-2 mitogen-activated protein kinases, can be modulated by CD94 NK receptors. Therefore, it appears that V{gamma}9V{delta}2 T cells can be physiologically activated by two sequential steps via two different cell surface Ags: the TCR-CD3 complex and the Fc{gamma}RIIIA receptor, which are specific cell surface Ags for T lymphocytes and NK cells, respectively. This strongly suggests that, in the general scheme of the immune response, V{gamma}9V{delta}2 T cells represent an important subpopulation of cells that play a key role in the defense against invading pathogens.




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