SEARCH:   Advanced

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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 21, 2004 Accepted June 15, 2005 Functional avidity directs T-cell fate in autoreactive CD4+ T-cells Roberto Mallone, Sharon A Kochik, Helena Reijonen, Bryan Carson, Steven F Ziegler, William Kwok, and Gerald T Nepom* Benaroya Research Institute at Virginia Mason, Seattle, WA, USA Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA * Corresponding author; email: jnepom{at}benaroyaresearch.org. MHC Class II tetramer staining and activation analysis identified two distinct types of antigen-specific CD4+ T-cells in the peripheral blood of human subjects 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 non-specific CD4+ T-cell responses. This suppression was contact-dependent, and correlated with the downregulation 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 paradoxical 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. 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]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020