{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:23:28Z","timestamp":1776842608857,"version":"3.51.2"},"reference-count":59,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Highly differentiated CD8+CD28\u2212CD27\u2212 T cells have short telomeres, defective telomerase activity, and reduced capacity for proliferation, indicating that they are close to replicative senescence. In addition, these cells express increased levels of the senescence-associated inhibitory receptor KLRG1 and have poor capacity for IL-2 synthesis and defective Akt (ser473) phosphorylation after activation. It is not known whether signaling via KLRG1 contributes to any of the attenuated differentiation-related functional changes in CD8+ T cells. To address this, we blocked KLRG1 signaling during T-cell receptor activation using antibodies against its major ligand, E-cadherin. This resulted in a significant enhancement of Akt (ser473) phosphorylation and T-cell receptor\u2013induced proliferative activity of CD8+CD28\u2212CD27\u2212 T cells. Furthermore, the increase of proliferation was directly linked to the Akt-mediated induction of cyclin D and E and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced telomerase activity in highly differentiated CD8+CD28\u2212CD27\u2212 T cells was not altered by KLRG1 blockade, indicating the involvement of other mechanisms. This is the first demonstration of a functional role for KLRG1 in primary human CD8+ T cells and highlights that certain functional defects that arise during progressive T-cell differentiation toward replicative senescence are maintained actively by inhibitory receptor signaling.<\/jats:p>","DOI":"10.1182\/blood-2009-01-199588","type":"journal-article","created":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T02:13:48Z","timestamp":1241144028000},"page":"6619-6628","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":214,"title":["KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells"],"prefix":"10.1182","volume":"113","author":[{"given":"Sian M.","family":"Henson","sequence":"first","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Ornella","family":"Franzese","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"},{"name":"Department of Neuroscience, University of Tor Vergata, Rome, Italy;"}]},{"given":"Richard","family":"Macaulay","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Valentina","family":"Libri","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Rita I.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"},{"name":"Department of Neuroscience, University of Tor Vergata, Rome, Italy;"},{"name":"Unidade de Immunologia Clinica, Instituto de Medicina Molecular, Lisbon, Portugal;"}]},{"given":"Sorena","family":"Kiani-Alikhan","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Fiona J.","family":"Plunkett","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Joanne E.","family":"Masters","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Sarah","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Stephen J.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Department Immunology, University College London, London, United Kingdom;"}]},{"given":"Hans-Peter","family":"Pircher","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany; and"}]},{"given":"Maria V. 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