SEARCH:   Advanced

Blood, 1 December 2008, Vol. 112, No. 12, pp. 4585-4590. Prepublished online as a Blood First Edition Paper on September 10, 2008; DOI 10.1182/blood-2008-06-165803. This Article Full Text (PDF) All Versions of this Article: blood-2008-06-165803v1 112/12/4585    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 Geiben-Lynn, R. Articles by Letvin, N. L. Search for Related Content PubMed PubMed Citation Articles by Geiben-Lynn, R. Articles by Letvin, N. L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 27, 2008 Accepted August 14, 2008 CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T cell immune responses Ralf Geiben-Lynn*, John R. Greenland, Kwesi Frimpong-Boateng, Nico van Rooijen, Avi-Hai Hovav, and Norman L. Letvin Viral Pathogenesis, BIDMC, Boston, MA, United States Department of Molecular Cell Biology, VUMC, Amsterdam, Netherlands * Corresponding author; email: rgeibenl{at}bidmc.harvard.edu. There is evidence that the limited immunogenicity of plasmid DNA vaccines is due at least in part to the rapid clearance of vaccine antigen expression by antigen-specific immune responses. However, the cell types responsible for the clearance of plasmid DNA vaccine antigens are not known. Here, we demonstrate that macrophages, NK cells, and CD8+ T cells did not significantly contribute to the DNA antigen clearance but CD4+ T cells played the crucial role in attenuating plasmid DNA vaccine antigen expression. Adoptive transfer experiments demonstrate that CD4+ T cells facilitated DNA vaccine antigen clearance in a Fas/FasL dependent manner. Furthermore, we show that depletion of CD4+ T cells prevented the clearance of vaccine antigen and the appearance of a CD8+ T cell immune response. Inoculation of MHC class II KO mice with the plasmid DNA led to persistent antigen expression and abolition of a CD8+ T cell immune response. Importantly, the prolongation of antigen expression by disrupting the CD4+ T cell Fas/FasL myocytes signaling led to a 3-5 fold increase of antigen-specific CD8+ T cell responses. These data demonstrate a dominant role of CD4+ T cell-mediated cytotoxicity in plasmid DNA vaccine antigen clearance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Geiben-Lynn, J. R. Greenland, K. Frimpong-Boateng, and N. L. Letvin Non-classical Natural Killer T Cells Modulate Plasmid DNA Vaccine Antigen Expression and Vaccine-elicited Immune Responses by MCP-1 Secretion after Interaction with a {beta}2-Microglobulin-independent CD1d J. Biol. Chem., December 4, 2009; 284(49): 33800 - 33806. [Abstract] [Full Text] [PDF] B. Poonia, M. S. Salvato, H. Yagita, T. Maeda, K. Okumura, and C. D. Pauza Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus Blood, August 6, 2009; 114(6): 1196 - 1204. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020