The Journal of Experimental Medicine
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Published online 21 May 2001.
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© The Rockefeller University Press, 0022-1007/2001/5/1221/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 10, May 21, 2001 1221-1226

Brief Definitive Report

Distinct Cytokine Profiles of Neonatal Natural Killer T Cells after Expansion with Subsets of Dendritic Cells

Norimitsu Kadowakia, Svetlana Antonenkoa, Stephen Hoa, Marie-Clotilde Rissoanb, Vassili Soumelisa, Steven A. Porcellic, Lewis L. Lanierd, and Yong-Jun Liua

a Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304
b Schering-Plough Corporation, Laboratory for Immunological Research, 69571 Dardilly, France
c Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461
d Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143
DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304.650-496-1200650-496-1157

yliu{at}dnax.org

Natural killer T (NKT) cells are a highly conserved subset of T cells that have been shown to play a critical role in suppressing T helper cell type 1–mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4–dependent manner. Thus, it is important to understand how the development of IL-4– versus interferon (IFN)-{gamma}–producing NKT cells is regulated. Here, we show that NKT cells from adult blood and those from cord blood undergo massive expansion in cell numbers (500–70,000-fold) during a 4-wk culture with IL-2, IL-7, phytohemagglutinin, anti-CD3, and anti-CD28 mAbs. Unlike adult NKT cells that preferentially produce both IL-4 and IFN-{gamma}, neonatal NKT cells preferentially produce IL-4 after polyclonal activation. Addition of type 2 dendritic cells (DC2) enhances the development of neonatal NKT cells into IL-4+IFN-{gamma}– NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4–IFN-{gamma}+ NKT1 cells. Adult NKT cells display limited plasticity for polarization induced by DC1 or DC2. Thus, newly generated NKT cells may possess the potent ability to develop into IL-4+IFN-{gamma}– NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-{gamma}.

Key Words: cord blood • interleukin 4 • interferon {gamma} • autoimmune diseases • graft versus host disease

N. Kadowaki's present address is Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

© 2001 The Rockefeller University Press


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