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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-05-1389. This Article Full Text (PDF) All Versions of this Article: 2002-05-1389v1 100/12/4108    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Feng, H. Articles by Katsanis, E. Search for Related Content PubMed PubMed Citation Articles by Feng, H. Articles by Katsanis, E. Social Bookmarking                   What's this? Submitted May 22, 2002 Accepted July 9, 2002 Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells Hanping Feng, Yi Zeng, Michael W Graner, and Emmanuel Katsanis* Department of Pediatrics, University of Arizona, Tucson, AZ, USA * Corresponding author; email: katsanis{at}peds.arizona.edu. We have previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than non-stressed ones. Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells (BCR-ABL+) express HSP60 and HSP72 on their surface. To explore how the immune system distinguishes stressed from non-stressed apoptotic tumor cells, we analyzed the responses of dendritic cells to these two types of apoptotic cells. We found that non-stressed and heat-stressed apoptotic 12B1-D1 cells were taken up by dendritic cells in a comparable fashion. However, when stressed apoptotic 12B1-D1 cells were co-incubated with immature dendritic cells for 24 hours, this resulted in greater upregulation of co-stimulatory molecules (CD40, CD80, and CD86) on the surface of dendritic cells. Moreover, stressed apoptotic 12B1-D1 cells were more effective in stimulating dendritic cells to secrete IL-12, and in enhancing their immunostimulatory functions in mixed leukocyte reactions. Furthermore, we demonstrated that immunization of mice with stressed apoptotic 12B1-D1 cells induced the secretion of TH1 profile of cytokines by spleen cells. Splenocytes from mice immunized with stressed apoptotic cells, but not non-stressed ones, were capable of lysing 12B1-D1 and the parental 12B1 line, but not a B cell leukemia line, A20. Our data indicate that stressed apoptotic tumor cells are capable of providing the necessary danger signals, likely through increased surface expression of HSPs, resulting in activation/maturation of dendritic cells, and ultimately the generation of potent antitumor T-cell responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Kushwah, J. R. Oliver, J. Zhang, K. A. Siminovitch, and J. Hu Apoptotic Dendritic Cells Induce Tolerance in Mice through Suppression of Dendritic Cell Maturation and Induction of Antigen-Specific Regulatory T Cells J. Immunol., December 1, 2009; 183(11): 7104 - 7118. [Abstract] [Full Text] [PDF] I. A. Parish, J. Waithman, G. M. Davey, G. T. Belz, J. D. Mintern, C. Kurts, R. M. Sutherland, F. R. Carbone, and W. R. Heath Tissue destruction caused by cytotoxic T lymphocytes induces deletional tolerance PNAS, March 10, 2009; 106(10): 3901 - 3906. 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