Late IL-2 signals limit effector CD4 T cell contraction and serve as a checkpoint for transition to memory

Abstract

Event Abstract Back to Event Late IL-2 signals limit effector CD4 T cell contraction and serve as a checkpoint for transition to memory Karl K. Mckinstry1*, Tara M. Strutt1, Andrea Cooper2 and Susan Swain1 1 University of Massachusetts Medical School, Pathology, United States 2 Trudeau Institute, United States Pathogen challenge causes the dramatic expansion of responding T cells resulting in large populations of activated effector cells at both secondary lymphoid sites where they originate, and at sites of infection and inflammation to which they migrate. Following the resolution of infection, most effector cells undergo apoptosis in the process known as ‘contraction’, while a cohort escapes death, transitions to a resting memory state, and persists for extended periods to provide long-term immunity. The factors and mechanisms determining the extent of T cell contraction and the efficiency of memory generation are unclear. We find that late, autocrine IL-2 during a narrow timeframe is required to limit the contraction of highly-differentiated CD4 T cell effectors generated by influenza A virus (IAV). We validate key findings by restoring IL-2 signals to IL-2-deficient CD4 T cells responding in wild type (WT) hosts, and by short-term neutralization of IL-2 in recipients of WT IAV-specific donor cells. Interestingly, late IL-2 is required to rescue effectors generated from both naïve and memory precursors from enhanced contraction. One of the few differences that distinguish WT and IL-2-deficient effectors at the peak of their response is higher expression of IL-7 receptor by WT cells. We find that late IL-2 is required for effectors to permanently increase IL-7 receptor expression, allowing ambient IL-7 to limit excessive contraction and to sustain their long-term persistence in the lung and in secondary lymphoid organs. This establishes a late IL-2-dependent checkpoint for memory CD4 T cell generation, with important implications for vaccine design. Acknowledgements This work was supported by NIH grants AI-46530 and NS-061014. Keywords: T cell memory, CD4 T cell, Influenza A virus, Cytokines, Interleukin-2 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Mckinstry KK, Strutt TM, Cooper A and Swain S (2013). Late IL-2 signals limit effector CD4 T cell contraction and serve as a checkpoint for transition to memory. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01203 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: 12 Sep 2013; Published Online: 19 Sep 2013. * Correspondence: Dr. Karl K Mckinstry, University of Massachusetts Medical School, Pathology, Worcester, Massachusetts, United States, kai.mckinstry@ucf.edu 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 Karl K Mckinstry Tara M Strutt Andrea Cooper Susan Swain Google Karl K Mckinstry Tara M Strutt Andrea Cooper Susan Swain Google Scholar Karl K Mckinstry Tara M Strutt Andrea Cooper Susan Swain PubMed Karl K Mckinstry Tara M Strutt Andrea Cooper Susan Swain 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.