The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kunisaki, Y.
Right arrow Articles by Fukui, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kunisaki, Y.
Right arrow Articles by Fukui, Y.
The Journal of Immunology, 2006, 176: 4640-4645.
Copyright © 2006 by The American Association of Immunologists

DOCK2 Is Required in T Cell Precursors for Development of V{alpha}14 NK T Cells1

Yuya Kunisaki*, Yoshihiko Tanaka*, Terukazu Sanui*, Ayumi Inayoshi*,{dagger}, Mayuko Noda*,{dagger}, Toshinori Nakayama{ddagger}, Michishige Harada§, Masaru Taniguchi§, Takehiko Sasazuki and Yoshinori Fukui2,*,{dagger}

* Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; {dagger} Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Japan; {ddagger} Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; § Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; and International Medical Center of Japan, Tokyo, Japan

Mouse CD1d-restricted V{alpha}14 NKT cells are a unique subset of lymphocytes, which play important roles in immune regulation, tumor surveillance and host defense against pathogens. DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster myoblast city, is critical for lymphocyte migration and regulates T cell responsiveness through immunological synapse formation, yet its role in V{alpha}14 NKT cells remains unknown. We found that DOCK2 deficiency causes marked reduction of V{alpha}14 NKT cells in the thymus, liver, and spleen. When {alpha}-galactosylceramide ({alpha}-GalCer), a ligand for V{alpha}14 NKT cells, was administrated, cytokine production was scarcely detected in DOCK2-deficient mice, suggesting that DOCK2 deficiency primarily affects generation of V{alpha}14 NKT cells. Supporting this idea, staining with CD1d/{alpha}-GalCer tetramers revealed that CD44–NK1.1– V{alpha}14 NKT cell precursors are severely reduced in the thymuses of DOCK2-deficient mice. In addition, studies using bone marrow chimeras indicated that development of V{alpha}14 NKT cells requires DOCK2 expression in T cell precursors, but not in APCs. These results indicate that DOCK2 is required for positive selection of V{alpha}14 NKT cells in a cell-autonomous manner, thereby suggesting that avidity-based selection also governs development of this unique subset of lymphocytes in the thymus.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
P. J. Cimino, I. Sokal, J. Leverenz, Y. Fukui, and T. J. Montine
DOCK2 Is a Microglial Specific Regulator of Central Nervous System Innate Immunity Found in Normal and Alzheimer's Disease Brain
Am. J. Pathol., October 1, 2009; 175(4): 1622 - 1630.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. B. Au-Yeung and D. J. Fowell
A Key Role for Itk in Both IFN{gamma} and IL-4 Production by NKT Cells
J. Immunol., July 1, 2007; 179(1): 111 - 119.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.