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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1801-1807.
Prepublished online as a Blood First Edition Paper on June 3, 2004; DOI 10.1182/blood-2004-01-0331.


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IMMUNOBIOLOGY

Fc{gamma}RIII discriminates between 2 subsets of V{gamma}9V{delta}2 effector cells with different responses and activation pathways

Daniela F. Angelini, Giovanna Borsellino, Mary Poupot, Adamo Diamantini, Rémy Poupot, Giorgio Bernardi, Fabrizio Poccia, Jean-Jacques Fournié, and Luca Battistini

From the Neuroimmunology Unit, Santa Lucia Foundation, Scientific Institute (IRCCS), Rome, Italy; the Départment Oncogénèse et Signalisation dans les Cellules Hématopoiétiques, Unité 563 de l'Institut National de la Santé etdela Recherche Médicale, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; the Department of Neuroscience, University of Rome "Tor Vergata," and the Laboratory of Immunopathology, Padiglione Del Vecchio, National Institute for Infectious Diseases, Rome, Italy.

Upon recognition of nonpeptidic phosphoantigens, human V{delta}2 T lymphocytes enter a lineage differentiation pattern that determines the generation of memory cells with a range of effector functions. Here, we show that within the effector memory V{delta}2 population, 2 distinct and complementary subsets with regard to phenotype, mode of activation, and type of responses can be identified: V{delta}2 TEMh cells, which express high levels of chemokine receptors, but low levels of perforin and of natural killer receptors (NKRs) and which produce large amounts of interferon {gamma} (IFN-{gamma}) and tumor necrosis factor {alpha} (TNF-{alpha}) in response to T-cell receptor (TCR)–specific stimulation by phosphoantigens; and V{delta}2TEMRA cells, which constitutively express several NKRs, high amounts of perforin, but low levels of chemokine receptors and of IFN-{gamma}. These NK-like cells are refractory to phosphoantigen but respond to activation via Fc{gamma}RIII (CD16) and are highly active against tumoral target cells. Thus, circulating V{delta}2T lymphocytes comprise 2 functionally diverse subsets of effector memory cells that may be discriminated on the basis of CD16 expression.


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