Human memory T-cell subsets require distinct costimulatory signals to efficiently expand ex vivo

Abstract

Event Abstract Back to Event Human memory T-cell subsets require distinct costimulatory signals to efficiently expand ex vivo Valentina Volpin1, 2*, Nicoletta Cieri1, 2 and Chiara Bonini1 1 San Raffaele Scientific Institute, Italy 2 Università Vita-Salute San Raffaele, Italy Costimulation plays a critical role for activation of T cells in response to pathogens, cancer and in alloreactive immune responses. However, costimulatory requirements of memory T cell responses have been much less studied than those for primary response generation, especially in humans. In the present work, we evaluated the ability of several costimulatory molecules (the CD28-family member CD28 and ICOS, and the TNFR-family members 4-1BB, OX40, GITR, CD27, CD30, HVEM) in expanding ex-vivo human memory T-cell subsets. We assessed the effect of these costimulatory molecules on central memory (TCM), effector memory (TEM) and on the recently identified memory stem T cells (TSCM). Memory T-cell subsets were FACS-sorted, according to the expression of CD45RA/CD62L and CD95, activated by coated anti-CD3 antibody in the presence of anti-costimulatory molecules antibodies and cultured with low dose homeostatic cytokines. The efficacy of costimulatory molecules was measured in terms of T-cell expansion and preservation of the original surface phenotype. Strikingly, we found that each memory T-cell subset best responded to distinct costimulatory signals. TSCM lymphocytes expanded, while maintaining a higher fraction of cells with the original and less-differentiated phenotype, when stimulated in the presence of OX-40- and GITR-mediated signals, while TCM best performed when CD28- and 4-1BB-costimulated. Finally, TEM cells expanded to higher numbers in response to CD27 costimulation. We are currently evaluating the cytokine secretion profile of differentially costimulated T-cell subsets. Altogether, these findings may help in designing new strategies to boost immunity against immune-evading pathogens and tumors, as well as to increase vaccine efficacy. Keywords: T-cell memory subsets, costimulations, Immunotherapy, T-cell expansion, recall responses Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Volpin V, Cieri N and Bonini C (2013). Human memory T-cell subsets require distinct costimulatory signals to efficiently expand ex vivo. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00999 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Valentina Volpin, San Raffaele Scientific Institute, Milan, Italy, volpin.valentina@hsr.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Valentina Volpin Nicoletta Cieri Chiara Bonini Google Valentina Volpin Nicoletta Cieri Chiara Bonini Google Scholar Valentina Volpin Nicoletta Cieri Chiara Bonini PubMed Valentina Volpin Nicoletta Cieri Chiara Bonini Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.