Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice

Proceedings of the National Academy of Sciences of the United States of America
Kylie M QuinnNicole L La Gruta

Abstract

In advanced age, decreased CD8(+) cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naïve CTL precursors (CTLp). Although the age-related fall in CD8(+) T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naïve CD8(+) T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8(+) T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naïve C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8(+) T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, nonrandom alterations in TCR usag...Continue Reading

References

Dec 22, 1998·The Journal of Experimental Medicine·H S AzzamP E Love
Jun 5, 2002·Mechanisms of Ageing and Development·John Leander Z PoDonna M Murasko
Mar 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Katherine KedzierskaPeter C Doherty
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole L La GrutaPeter C Doherty
Jan 16, 2007·Experimental Gerontology·Jörg J GoronzyCornelia M Weyand
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul G ThomasPeter C Doherty
Feb 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicole L La GrutaStephen J Turner
Jan 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mushtaq AhmedMarcia A Blackman
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vilma DecmanE John Wherry
May 5, 2010·The Journal of Clinical Investigation·Nicole L La GrutaStephen J Turner
Sep 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·H Hamlet ChuMarc K Jenkins
Dec 8, 2010·The Journal of Clinical Investigation·Pradyot DashPaul G Thomas
Aug 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Brian D RuddJanko Nikolich-Žugich
Jan 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vilma DecmanE John Wherry
Feb 7, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adovi D AkueStephen C Jameson
Mar 3, 2012·PLoS Pathogens·Sophie A ValkenburgKatherine Kedzierska
Apr 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc K Jenkins, James J Moon
Mar 12, 2013·Experimental Gerontology·Jiu JiangDonna M Murasko
Nov 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bo-Chin ChiuStephen W Chensue
Dec 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristin R RenkemaJanko Nikolich-Žugich
Apr 4, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tania CukalacNicole L La Gruta
Sep 7, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Janko Nikolich-Žugich
Oct 10, 2015·Nature Reviews. Immunology·David C TscharkeNicole L La Gruta

❮ Previous
Next ❯

Citations

Nov 11, 2017·Frontiers in Neuroscience·Serge Nataf
May 30, 2019·Immunology and Cell Biology·Tabinda Hussain, Kylie M Quinn
Nov 23, 2019·Genome Research·Jacob C KimmelAdam Z Rosenthal
Apr 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xavier Y X SngNicole L La Gruta
Jul 18, 2020·Journal of Leukocyte Biology·Kylie M QuinnMagdalena Plebanski
Jun 3, 2016·Science Translational Medicine·Shu-Qi ZhangNing Jiang
Oct 22, 2016·Clinical and Experimental Immunology·C KimJ J Goronzy
Apr 21, 2019·Medical Microbiology and Immunology·Mladen JergovićJanko Nikolich-Žugich
Dec 14, 2019·Clinical & Translational Immunology·Kylie M QuinnNicole L La Gruta
Jul 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Megan J SmitheyJanko Nikolich-Žugich
Jun 2, 2020·Frontiers in Immunology·Jennifer E CowanIzumi Ohigashi
Apr 25, 2017·Clinical & Translational Immunology·Thi Ho NguyenKatherine Kedzierska
Nov 20, 2020·International Journal of Molecular Sciences·Daniel ThieleTabinda Hussain
Apr 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alena MoudraOndrej Stepanek
Mar 3, 2021·Cold Spring Harbor Perspectives in Biology·Stephen J TurnerNicole L La Gruta
May 11, 2021·Frontiers in Immunology·Jayashree SrinivasanEllen R Richie
Jun 1, 2021·Frontiers in Immunology·Miguel Ángel Palacios-PedreroGiulietta Saletti
Aug 7, 2021·Nature Immunology·Hoyoung LeeEui-Cheol Shin
Aug 17, 2021·Cellular and Molecular Life Sciences : CMLS·Eliza Mari Kwesi-MaliepaardFred van Leeuwen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.