%0 Journal Article
%A Culina, Slobodan
%A Lalanne, Ana Ines
%A Afonso, Georgia
%A Cerosaletti, Karen
%A Pinto, Sheena
%A Sebastiani, Guido
%A Kuranda, Klaudia
%A Nigi, Laura
%A Eugster, Anne
%A Østerbye, Thomas
%A Maugein, Alicia
%A McLaren, James E
%A Ladell, Kristin
%A Larger, Etienne
%A Beressi, Jean-Paul
%A Lissina, Anna
%A Appay, Victor
%A Davidson, Howard W
%A Buus, Søren
%A Price, David A
%A Kuhn, Matthias
%A Bonifacio, Ezio
%A Battaglia, Manuela
%A Caillat-Zucman, Sophie
%A Dotta, Francesco
%A Scharfmann, Raphael
%A Kyewski, Bruno
%A Mallone, Roberto
%A Carel, Jean-Claude
%A Tubiana-Rufi, Nadia
%A Martinerie, Laetitia
%A Poidvin, Amélie
%A JacqzAigrain, Evelyne
%A Corvez, Laurence
%A Berruer, Véronique
%A Gautier, Jean-François
%A Baz, Baz
%A Haddadi, Nassima
%A Andreelli, Fabrizio
%A Amouyal, Chloé
%A Jaqueminet, Sophie
%A Bourron, Olivier
%A Dasque, Eric
%A Hartemann, Agnès
%A Lemoine-Yazigi, Amal
%A Dubois-Laforgue, Danièle
%A Travert, Florence
%A Feron, Marilyne
%A Rolland, Patrice
%A Vignali, Valérie
%A Marre, Michel
%A Chanson, Philippe
%A Briet, Claire
%A Guillausseau, Pierre-Jean
%A Ait-Bachir, Leila
%A Collet, Carole
%A Beziaud, Frédéric
%A Desforges-Bullet, Virginie
%A Petit-Aubert, Gwenaelle
%A Christin-Maitre, Sophie
%A Fève, Bruno
%A Vatier, Camille
%A Bourcigaux, Nathalie
%A Lautridou, Céline
%A Lahlou, Najiba
%A Bakouboula, Prissile
%A Elie, Caroline
%A Morel, Hélène
%A Treluyer, Jean-Marc
%A Gagnerault, Marie-Claude
%A Maillard, Claire
%A Jones, Anna
%T Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors.
%J Science immunology
%V 3
%N 20
%@ 2470-9468
%C Washington, DC
%I AAAS
%M DKFZ-2018-00722
%P eaao4013 -
%D 2018
%X The human leukocyte antigen-A2 (HLA-A2)-restricted zinc transporter 8186-194 (ZnT8186-194) and other islet epitopes elicit interferon-γ secretion by CD8+ T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8186-194-reactive CD8+ T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8+ T cells reactive to ZnT8186-194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8186-194-reactive CD8+ T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8186-194-reactive CD8+ T cell clonotypes were found to cross-recognize a Bacteroides stercoris mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8+ T cells. In contrast, ZnT8186-194-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8+ T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:29429978
%2 pmc:PMC5874133
%R 10.1126/sciimmunol.aao4013
%U https://inrepo02.dkfz.de/record/136022