Natural killer cells (NK-cells):

Family of innate lymphoid cells

Do not express antigen receptors: lineage markers CD3 and CD19 are negative


  • CD2, CD7, CD56, NCAM
  • Activating receptors: CD16, CD335, CD336, CD337
  • Inhibitory receptors: CD94/NKG2A, KIR/CD158
  • Variable CD11b, CD11c, CD38, CD45RA, CD45RO, HLA-DR, CD57 depending on activation status
    • Non-activated: CD2dim/-, CD7bright, CD38+, CD45RA+, CD45RO-, HLA-DR-, variable CD57, CD11c
  • Small CD2- CD5+ subsets can be seen in blood and spleen

2 subsets based on expression of CD16 and CD56

  • CD56dim CD16bright, KIR+, CD94heterogeneous, variable CD57, perforin, granzymeB: predominant in PB (90%), cytotoxic activity
  • CD56bright CD16-/dim, KIR-, CD94bright: mostly in lymphoid tissues (10% of circulating), influence immune response via release of cytokines

Normal NK-cell immunophenotype (bone marrow aspirate)

Natural_killer_cells_1 Natural_killer_cells_2 Natural_killer_cells_3

Normal NK-cell immunophenotype (peripheral blood)

Natural_killer_cells_4 Natural_killer_cells_5 Natural_killer_cells_6

Normal/reactive variations

  • Acute viral infections: higher CD38 and HLA-DR, decreased CD45RA co-expressed with CD45RO, homogeneously CD11c+, mostly CD57-
  • Chronic viral infections or neoplasia: late activating NK-cells
    • Positive CD57
    • Decreased CD7, CD38 and CD11b
    • Negative CD11c, HLA-DR, CD45RO

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