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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2798-2805. Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-12-4848. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4848v1 106/8/2798    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 Mallone, R. Articles by Nepom, G. T. Search for Related Content PubMed PubMed Citation Articles by Mallone, R. Articles by Nepom, G. T. Related Collections Apoptosis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Functional avidity directs T-cell fate in autoreactive CD4+ T cells Roberto Mallone, Sharon A. Kochik, Helena Reijonen, Bryan Carson, Steven F. Ziegler, William W. Kwok, and Gerald T. Nepom From the Benaroya Research Institute at Virginia Mason, Seattle, WA; and Department of Immunology, University of Washington School of Medicine, Seattle, WA. Major histocompatibility complex class II tetramer staining and activation analysis identified 2 distinct types of antigen-specific CD4+ T cells in the peripheral blood of humans with type 1 (autoimmune) diabetes. T cells with low-avidity recognition of peptide-MHC ligands had low sensitivity to activation and inefficient activation-induced apoptosis. In contrast, high-avidity T cells were highly sensitive to antigen-induced cell death through apoptotic mechanisms, and both apoptosis-resistant high- and low-avidity T cells that survived prolonged tetramer treatment were rendered anergic to restimulation by antigen. In addition, however, apoptosis-resistant high-avidity T cells acquired regulatory features, being able to suppress both antigen-specific and nonspecific CD4+ T-cell responses. This suppression was contact-dependent and correlated with the down-regulation of HLA class II and costimulatory molecules on antigen-presenting cells, including B cells and dendritic cells. T cells face a variety of fates following antigen exposure, including the paradoxic maintenance of high-avidity autoreactive T cells in the peripheral circulation, perhaps due to this capability of acquiring anergic and suppressive properties. Regulation via down-modulation of antigen-presenting cell function, a form of cell-to-cell licensing for suppression, also offers possibilities for the application of peptide-MHC therapeutics. (Blood. 2005;106:2798-2805) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Blancou, R. Mallone, E. Martinuzzi, S. Severe, S. Pogu, G. Novelli, G. Bruno, B. Charbonnel, M. Dolz, L. Chaillous, et al. Immunization of HLA Class I Transgenic Mice Identifies Autoantigenic Epitopes Eliciting Dominant Responses in Type 1 Diabetes Patients J. Immunol., June 1, 2007; 178(11): 7458 - 7466. [Abstract] [Full Text] [PDF]

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