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The Journal of Immunology, 2000, 165: 4917-4926.
Copyright © 2000 by The American Association of Immunologists

A Subset of NKT Cells That Lacks the NK1.1 Marker, Expresses CD1d Molecules, and Autopresents the {alpha}-Galactosylceramide Antigen1

Agathe Hameg*, Irina Apostolou{dagger}, Maria Leite-de-Moraes{ddagger}, Jean-Marc Gombert§, Corinne Garcia, Yasuhiko Koezuka||, Jean-François Bach* and André Herbelin2,*

* Institut National de La Santé et de la Recherche Médicale (INSERM) Unité 25 and Centre Claude Bernard, Hôpital Necker, Paris, France; {dagger} INSERM Unité 277, Institut Pasteur, Paris, France; {ddagger} Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8603, Université René Descartes, Hôpital Necker, Paris, France; § Laboratoire d’Immunologie-Immunopathologie, Centre Hospitalier Universitaire, Poitiers, France; INSERM Unité 373, Institut Necker, Paris, France; and || Pharmaceutical Research Laboratory, Kirin Brewery Company, Gunma, Japan

In the present report, we characterize a novel T cell subset that shares with the NKT cell lineage both CD1d-restriction and high reactivity in vivo and in vitro to the {alpha}-galactosylceramide ({alpha}-GalCer) glycolipid. These cells preferentially use the canonical V{alpha}14-J{alpha}281 TCR-{alpha}-chain and Vß8 TCR-ß segments, and are stimulated by {alpha}-GalCer in a CD1d-dependent fashion. However, in contrast to classical NKT cells, they lack the NK1.1 marker and express high surface levels of CD1d molecules. In addition, this NK1.1- CD1dhigh T subset, further referred to as CD1dhigh NKT cells, can be distinguished by its unique functional features. Although NK1.1+ NKT cells require exogenous CD1d-presenting cells to make them responsive to {alpha}-GalCer, CD1dhigh NKT cells can engage their own surface CD1d in an autocrine and/or paracrine manner. Furthermore, in response to {alpha}-GalCer, CD1dhigh NKT cells produce high amounts of IL-4 and moderate amounts of IFN-{gamma}, a cytokine profile more consistent with a Th2-like phenotype rather than the Th0-like phenotype typical of NK1.1+ NKT cells. Our work reveals a far greater level of complexity within the NKT cell population than previously recognized and provides the first evidence for T cells that can be activated upon TCR ligation by CD1d-restricted recognition of their ligand in the absence of conventional APCs.




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