The Journal of Experimental Medicine
StemCell Technologies
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 4 August 2003. doi:10.1084/jem.20030584
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
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 Gao, Y.
Right arrow Articles by Yin, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gao, Y.
Right arrow Articles by Yin, Z.
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?
© Rockefeller University Press, 0022-1007/2003/8/433 $5.00
The Journal of Experimental Medicine, Volume 198, Number 3, 433-442

{gamma}{delta} T Cells Provide an Early Source of Interferon {gamma} in Tumor Immunity

Yunfei Gao1, Wancai Yang4, Meng Pan1, Eileen Scully1, Michael Girardi2, Leonard H. Augenlicht4, Joe Craft1,3 and Zhinan Yin1

1 Section of Rheumatology, Department of Medicine
2 Department of Dermatology, Yale School of Medicine, New Haven, CT 06520
3 Section of Immunobiology, Yale School of Medicine, New Haven, CT 06520
4 Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY 10467

Address correspondence to Zhinan Yin, Section of Rheumatology, Yale School of Medicine, 300 Cedar Street, CAB Building Room S517, New Haven, CT 06520. Phone: 203-737-2772; Fax: 203-785-7053; email: zhinan.yin{at}yale.edu

Interferon (IFN)-{gamma} is necessary for tumor immunity, however, its initial cellular source is unknown. Because {gamma}{delta} T cells primarily produce this cytokine upon activation, we hypothesized that they would provide an important early source of IFN-{gamma} in tumor immunosurveillance. To address this hypothesis, we first demonstrated that {gamma}{delta} T cell–deficient mice had a significantly higher incidence of tumor development after challenge with a chemical carcinogen methylcholanthrene (MCA) or inoculation with the melanoma cell line B16. In wild-type mice, {gamma}{delta} T cells were recruited to the site of tumor as early as day 3 after inoculation, followed by {alpha}ß T cells at day 5. We then used bone marrow chimeras and fetal liver reconstitutions to create mice with an intact {gamma}{delta} T cell repertoire but one that was specifically deficient in the capacity to produce IFN-{gamma}. Such mice had a higher incidence of tumor development, induced either with MCA or by inoculation of B16 melanoma cells, compared with mice with IFN-{gamma}–competent {gamma}{delta} T cells. Moreover, genetic deficiency of {gamma}{delta} T cells resulted in impaired IFN-{gamma} production by tumor antigen-triggered {alpha}ß T cell upon immunization with tumor lysate. These results demonstrate that {gamma}{delta} T cells can play a necessary role in tumor immunity through provision of an early source of IFN-{gamma} that in turn may regulate the function of tumor-triggered {alpha}ß T cells.

Key Words: cytokines • immunosurveillance • immune regulation • tumor immunosurveillance


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