Pou6f1 is dispensable for mouse T cell development and virus-specific memory CD8+ T cell generation

Abstract

Event Abstract Back to Event Pou6f1 is dispensable for mouse T cell development and virus-specific memory CD8+ T cell generation Marlene J. Carrasco-Alfonso1*, Wenyu Jiang1 and John Luckey1* 1 Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, United States Pou6f1 is a POU-domain transcription factor whose paralogs control self-renewal (e.g. Oct-4) and cell fate determination (e.g. Pit-1, Brn3a). It has been shown to be selectively upregulated at the DN3a to DP stages in thymocytes; and across different models in antigen-specific memory/memory-precursors relative to shorter-lived mature CD8+ T lymphocytes. On these bases, we hypothesized that it is required for maintaining a multipotent and/or differentiation-poised state in T cells. To test this, we quantitatively validated its differential expression in lymphocytes, and generated and characterized conditional (Cre/loxP-based) Pou6f1 knockout mice. Germ-line deletion (EIIa-Cre-driven) resulted in viable and fertile progeny with no obvious morphological or behavioral abnormalities. Mice with an early deletion in thymocytes (Lck-Cre-driven) showed normal numbers and phenotype of thymic populations (DN, DP, SP4 and SP8) and peripheral CD4+ and CD8+ T cells, according to the expression of TCRβ, CD3, and activation (CD5, CD44, CD69), differentiation (CD25, CD27, CD28, CD62L, CD122), survival (CD127) and senescence (Klrg1) markers. Likewise, specific deletion in CD8+ cells (E8I/CD8a-Cre-driven) did not affect either antigen-specific CD8+ T cell effector response (ex-vivo OVA-induced IFN-γ synthesis), or memory generation (pentamer binder frequency) and response upon infection with vaccinia-OVA virus. The effects on both memory formation in a competitive adoptive transfer setting and secondary responses are under study. In conclusion, this is the first description of a Pou6f1 knockout mouse. Results to date suggest that Pou6f1 may not be involved in lineage commitment of thymocytes or CD8+ T lymphocytes, or that in the current experimental models its loss is compensated. Keywords: Pou6f1, CD8+ T cell memory, T cell development, POU-domain transcription factor, conditional knockout Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Carrasco-Alfonso MJ, Jiang W and Luckey J (2013). Pou6f1 is dispensable for mouse T cell development and virus-specific memory CD8+ T cell generation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01013 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: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Marlene J Carrasco-Alfonso, Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, Boston, MA, 02115, United States, marleneca@hotmail.com Dr. John Luckey, Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, Boston, MA, 02115, United States, cluckey@partners.org 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 Marlene J Carrasco-Alfonso Wenyu Jiang John Luckey Google Marlene J Carrasco-Alfonso Wenyu Jiang John Luckey Google Scholar Marlene J Carrasco-Alfonso Wenyu Jiang John Luckey PubMed Marlene J Carrasco-Alfonso Wenyu Jiang John Luckey 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.