Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood

J Immunol. 2013 Aug 15;191(4):1625-36. doi: 10.4049/jimmunol.1300111. Epub 2013 Jul 15.


Killer cell Ig-like receptors (KIRs) on NK cells have been linked to a wide spectrum of health conditions such as chronic infections, autoimmune diseases, pregnancy complications, cancers, and transplant failures. A small subset of effector memory T cells also expresses KIRs. In this study, we use modern analytic tools including genome-wide and multiplex molecular, phenotypic, and functional assays to characterize the KIR(+) T cells in human blood. We find that KIR(+) T cells primarily reside in the CD56(+) T population that is distinctively DNAM-1(high) with a genome-wide quiescent transcriptome, short telomere, and limited TCR excision circles. During CMV reactivation in bone marrow transplant recipients, KIR(+)CD56(+) T cells rapidly expanded in real-time but not KIR(+)CD56(-) T cells or KIR(+) NK cells. In CMV(+) asymptomatic donors, as much as 50% of CD56(+) T cells are KIR(+), and most are distinguishably KIR2DL2/3(+)NKG2C(+)CD57(+). Functionally, the KIR(+)CD56(+) T cell subset lyses cancer cells and CMVpp65-pulsed target cells in a dual KIR-dependent and TCR-dependent manner. Analysis of metabolic transcriptome confirms the immunological memory status of KIR(+)CD56(+) T cells in contrast to KIR(-)CD56(+) T cells that are more active in energy metabolism and effector differentiation. KIR(-)CD56(+) T cells have >25-fold higher level of expression of RORC than the KIR(+) counterpart and are a previously unknown producer of IL-13 rather than IL-17 in multiplex cytokine arrays. Our data provide fundamental insights into KIR(+) T cells biologically and clinically.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Asymptomatic Diseases
  • Bone Marrow Transplantation
  • CD56 Antigen / analysis
  • CD57 Antigens / analysis
  • Cell Line, Tumor
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / immunology
  • Cytotoxicity, Immunologic
  • Genome-Wide Association Study
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / immunology*
  • Metabolome
  • Multiplex Polymerase Chain Reaction
  • NK Cell Lectin-Like Receptor Subfamily C / analysis
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, KIR / analysis
  • Receptors, KIR2DL2 / analysis
  • Receptors, KIR2DL3 / analysis
  • T-Lymphocyte Subsets / immunology*
  • Telomere / ultrastructure
  • Th17 Cells / immunology
  • Tissue Donors
  • Transcriptome
  • Virus Activation


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • CD56 Antigen
  • CD57 Antigens
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • KLRC2 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3

Associated data

  • GEO/GSE47855