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Mohammed, Rebar N.; Wehenkel, Sophie C.; Galkina, Elena V.; Yates, Emma-Kate; Preece, Graham; Newman, Andrew; Watson, H. Angharad; Ohme, Julia; Bridgeman, John S.; Durairaj, Ruban R. P.; Moon, Owen R.; Ladell, Kristin; Miners, Kelly L.; Dolton, Garry; Troeberg, Linda; Kashiwagi, Masahide; Murphy, Gillian; Nagase, Hideaki; Price, David A.; Matthews, R. James; Knäuper, Vera; Ager, Ann

ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells

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  • Medientyp: E-Artikel
  • Titel: ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells
  • Beteiligte: Mohammed, Rebar N.; Wehenkel, Sophie C.; Galkina, Elena V.; Yates, Emma-Kate; Preece, Graham; Newman, Andrew; Watson, H. Angharad; Ohme, Julia; Bridgeman, John S.; Durairaj, Ruban R. P.; Moon, Owen R.; Ladell, Kristin; Miners, Kelly L.; Dolton, Garry; Troeberg, Linda; Kashiwagi, Masahide; Murphy, Gillian; Nagase, Hideaki; Price, David A.; Matthews, R. James; Knäuper, Vera; Ager, Ann
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-019-41811-z
  • ISSN: 2045-2322
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naïve and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation<jats:italic>in vitro</jats:italic>which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity.</jats:p>
  • Zugangsstatus: Freier Zugang