The Journal of Experimental Medicine
MBL International Tel: 800.200.5459 CLICK HERE
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 8 March 2004 doi:10.1084/jem.20031981
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 879-884
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Street, S. E.A.
Right arrow Articles by Smyth, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Street, S. E.A.
Right arrow Articles by Smyth, M. J.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Brief Definitive Report

 Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and {gamma}{delta} T Cells

Shayna E.A. Street1, Yoshihiro Hayakawa1, Yifan Zhan2, Andrew M. Lew2, Duncan MacGregor3, Amanda M. Jamieson4, Andreas Diefenbach5, Hideo Yagita6, Dale I. Godfrey7, and Mark J. Smyth1

1 Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre (Peter Mac), 8006, Victoria, Australia
2 The Walter and Eliza Hall Institute of Medical Research, 3050, Victoria, Australia
3 The Department of Anatomical Pathology, The Austin and Repatriation Medical Centre, 3084, Heidelberg, Australia
4 Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720
5 Skirball Institute of Biomolecular Medicine, New York University, New York, NY 10016
6 Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan
7 Department of Microbiology and Immunology, University of Melbourne, Parkville, 3052, Victoria, Australia

Address correspondence to M.J. Smyth, Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre (Peter Mac), Locked Bag 1, A'Beckett St, 8006, Victoria, Australia. Phone: 61-3-9656-3728; Fax: 61-3-9656-1411; email: m.smyth{at}pmci.unimelb.edu.au

Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking ß-2 microglobulin (ß2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perforin gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked ß2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/ß2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perforin, but not IFN-{gamma}, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1+ and {gamma}{delta}TCR+ T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and {gamma}{delta}TCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.

Key Words: immunosurveillance • effector • NK cell • tumor • perforin

The online version of this article contains supplemental material.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS