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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1138-1146. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-05-023663. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-05-023663v1 109/3/1138    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 Heller, K. N. Articles by Munz, C. Search for Related Content PubMed PubMed Citation Articles by Heller, K. N. Articles by Munz, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 17, 2006 Accepted September 5, 2006 Distinct memory CD4+ T cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers Kevin N. Heller, Jenica Upshaw, Beza Seyoum, Henry Zebroski, and Christian Munz* Laboratory of Viral Immunobiology, Rockefeller University, New York, NY, USA Proteomics Resource Center, Rockefeller University, New York, NY, USA * Corresponding author; email: munzc{at}rockvax.rockefeller.edu. CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1 specific effector CD4+ T cells are primarily TH1 polarized. Here we show that most healthy EBV carriers have such IFN secreting EBNA1 specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory cell subsets. Despite continuous antigen presence due to persistent EBV infection half of the proliferating EBNA1 specific CD4+ T cells belonged to the central memory compartment (TCM). The remaining EBNA1 specific CD4+ T cells displayed an effector memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1 specific TCM CD4+ T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1 polarized effector cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Gurer, T. Strowig, F. Brilot, M. Pack, C. Trumpfheller, F. Arrey, C. G. Park, R. M. Steinman, and C. Munz Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses Blood, August 15, 2008; 112(4): 1231 - 1239. [Abstract] [Full Text] [PDF] J. D. Lunemann, I. Jelcic, S. Roberts, A. Lutterotti, B. Tackenberg, R. Martin, and C. Munz EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-{gamma} and IL-2 J. Exp. Med., August 4, 2008; 205(8): 1763 - 1773. [Abstract] [Full Text] [PDF] J. D. Lunemann, O. Frey, T. Eidner, M. Baier, S. Roberts, J. Sashihara, R. Volkmer, J. I. Cohen, G. Hein, T. Kamradt, et al. Increased Frequency of EBV-Specific Effector Memory CD8+ T Cells Correlates with Higher Viral Load in Rheumatoid Arthritis J. Immunol., July 15, 2008; 181(2): 991 - 1000. [Abstract] [Full Text] [PDF] S. Bhaduri-McIntosh, M. J. Rotenberg, B. Gardner, M. Robert, and G. Miller Repertoire and frequency of immune cells reactive to Epstein-Barr virus-derived autologous lymphoblastoid cell lines Blood, February 1, 2008; 111(3): 1334 - 1343. [Abstract] [Full Text] [PDF]

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