Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 183K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sauter, B. Articles by Bhardwaj, N. Search for Related Content PubMed PubMed Citation Articles by Sauter, B. Articles by Bhardwaj, N. Pubmed/NCBI databases Medline Plus Health Information Cancer Social Bookmarking                            What's this?

Original Article

Birthe Sauter^a, Matthew L. Albert^a, Loise Francisco^a, Marie Larsson^a, Selin Somersan^a, and Nina Bhardwaj^a

^a Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021
the Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021.212-327-8875212-327-8332

bhardwn{at}rockvax.rockefeller.edu

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4⁺ and CD8⁺ T cells. Cross-presentation of antigens to CD8⁺ T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.

Key Words: dendritic cells • apoptosis • necrosis • cross-presentation • ELISPOT assay

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Kushwah, R., Oliver, J. R., Zhang, J., Siminovitch, K. A., Hu, J. (2009). Apoptotic Dendritic Cells Induce Tolerance in Mice through Suppression of Dendritic Cell Maturation and Induction of Antigen-Specific Regulatory T Cells. J. Immunol. 183: 7104-7118 [Abstract] [Full Text]  
• Wang, Y.-s., Li, D., Shi, H.-s., Wen, Y.-j., Yang, L., Xu, N., Chen, X.-c., Chen, X., Chen, P., Li, J., Deng, H.-x., Wang, C.-t., Xie, G., Huang, S., Mao, Y.-q., Chen, L.-j., Zhao, X., Wei, Y.-q. (2009). Intratumoral Expression of Mature Human Neutrophil Peptide-1 Mediates Antitumor Immunity in Mice. Clin. Cancer Res. 15: 6901-6911 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS