• Open Access

CD6 attenuates early and late signaling events, setting thresholds for T-cell activation

Authors

  • Marta I. Oliveira,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    2. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
    Search for more papers by this author
  • Carine M. Gonçalves,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    2. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
    Search for more papers by this author
  • Mafalda Pinto,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    Search for more papers by this author
  • Stéphanie Fabre,

    1. Institut National de la Santé et de la Recherche Médicale, Paris, France
    2. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
    Search for more papers by this author
  • Ana Mafalda Santos,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    2. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
    3. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
    Search for more papers by this author
  • Simon F. Lee,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    Search for more papers by this author
  • Mónica A. A. Castro,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    Search for more papers by this author
  • Raquel J. Nunes,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    2. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
    Search for more papers by this author
  • Rita R. Barbosa,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    Search for more papers by this author
  • Jane R. Parnes,

    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
    Current affiliation:
    1. Amgen Inc., Thousand Oaks, CA 91320, USA
    Search for more papers by this author
  • Chao Yu,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
    Search for more papers by this author
  • Simon J. Davis,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
    Search for more papers by this author
  • Alexandra Moreira,

    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    Search for more papers by this author
  • Georges Bismuth,

    1. Institut National de la Santé et de la Recherche Médicale, Paris, France
    2. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
    Search for more papers by this author
  • Alexandre M. Carmo

    Corresponding author
    1. Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal
    2. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
    • Institute for Molecular and Cellular Biology, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal Fax: +351-226099157

    Search for more papers by this author

Abstract

The T lineage glycoprotein CD6 is generally considered to be a costimulator of T-cell activation. Here, we demonstrate that CD6 significantly reduces early and late T-cell responses upon superantigen stimulation or TCR triggering by Abs. Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor. When the cytoplasmic domain of rat CD6 was removed, calcium responses were recovered, indicating that the inhibitory properties of CD6 are attributable to its cytoplasmic domain. Calcium responses, and also late indicators of T-cell activation such as IL-2 release, were also diminished in TCR-activated Jurkat cells expressing human CD6, compared with CD6-deficient cells or cells expressing a cytoplasmic deletion mutant of human CD6. Similarly, calcium signals triggered by anti-CD3 were enhanced in human T lymphocytes following morpholino-mediated suppression of CD6 expression. Finally, the proliferation of T lymphocytes was increased when the CD6–CD166 interaction was blocked with anti-CD166 Abs, but inhibited when anti-CD6 Abs were used. Our data suggest that CD6 is a signaling attenuator whose expression alone, i.e. in the absence of ligand engagement, is sufficient to restrain signaling in T cells.

Ancillary