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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1249-1258. Prepublished online as a Blood First Edition Paper on June 6, 2008; DOI 10.1182/blood-2007-09-114389. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-114389v1 112/4/1249    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Helft, J. Articles by Lantz, O. Search for Related Content PubMed PubMed Citation Articles by Helft, J. Articles by Lantz, O. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antigen-specific T-T interactions regulate CD4 T-cell expansion Julie Helft1,2, Alexandra Jacquet1,2, Nathalie T. Joncker1,2, Isabelle Grandjean1,2, Guillaume Dorothée1,2, Adrien Kissenpfennig35, Bernard Malissen35, Polly Matzinger6, and Olivier Lantz1,2 1 Laboratoire d'Immunologie clinique, 2 Inserm U653, Institut Curie, Paris; 3 Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Marseille; 4 Inserm U631, Marseille; 5 Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille, France; and 6 The Ghost Lab, Laboratory of Cellular and Molecular Immunology (LCMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD The regulation of CD4 T-cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel mechanism of T-cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a negative feedback loop by capturing their cognate major histocompatibility class (MHC)/peptide complexes from Ag-presenting cells and presenting them to Ag-experienced CD4 T cells, thereby inhibiting their recruitment into the response while allowing recruitment of naive T cells. The inhibition is Ag specific, begins at day 2 (long before Ag disappearance), and cannot be overcome by providing new Ag-loaded dendritic cells. In this way, CD4 T-cell proliferation is regulated in a functional relationship to the amount of Ag, while allowing naive T cells to generate repertoire variety. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. N. M. Nolte-'t Hoen, S. I. Buschow, S. M. Anderton, W. Stoorvogel, and M. H. M. Wauben Activated T cells recruit exosomes secreted by dendritic cells via LFA-1 Blood, February 26, 2009; 113(9): 1977 - 1981. [Abstract] [Full Text] [PDF] W. F. N. Chan, H. Razavy, and C. C. Anderson Differential Susceptibility of Allogeneic Targets to Indirect CD4 Immunity Generates Split Tolerance J. Immunol., October 1, 2008; 181(7): 4603 - 4612. [Abstract] [Full Text] [PDF]

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