Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

Authors

  • Hojjatollah N. Charoudeh,

    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Grzegorz Terszowski,

    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Karol Czaja,

    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Search for more papers by this author
  • Asensio Gonzalez,

    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Search for more papers by this author
  • Karin Schmitter,

    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Search for more papers by this author
  • Martin Stern

    Corresponding author
    1. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    • Full correspondence: Prof. Martin Stern, Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland

      Fax: +41-61-265-44 50

      e-mail: sternm@uhbs.ch

    Search for more papers by this author

Abstract

Patients carrying activating killer cell immunoglobulin-like receptor (KIR) genes are significantly protected from CMV-associated complications after solid organ or hematopoietic stem cell transplantation. Whether previous infection with CMV affects NK-cell function in healthy donors is unknown. We studied the KIR repertoire and alterations of KIR expression after in vitro exposure to CMV in 54 healthy donors. The expression of neither activating nor inhibitory KIRs was different at baseline between 23 seropositive and 31 seronegative donors. However, after co-culture of NK cells with CMV-infected fibroblast cells, expression of the inhibitory receptors KIR2DL1 and KIR2DL3 and the activating receptor KIR3DS1 significantly increased in CMV-seropositive donors. In CMV-seronegative donors, changes were subtle and restricted to the subset of NK cells expressing NK-cell group antigen 2C (NKG2C). Expansion of inhibitory KIRs occurred exclusively in donors carrying the cognate HLA class I ligands, whereas the presence of the putative ligand HLA-Bw4 was not necessary for the expansion of KIR3DS1-expressing NK cells. Our data show that previous infection with CMV does not alter the resting NK-cell receptor repertoire, but appears to modify how NK cells respond to re-exposure to CMV in vitro.

Ancillary