Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties

Blood Cells Mol Dis. Jul-Aug 2001;27(4):731-43. doi: 10.1006/bcmd.2001.0443.


In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK-lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK-cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, Differentiation / analysis*
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • CD56 Antigen / analysis*
  • Cell Adhesion Molecules / analysis
  • Cell Differentiation
  • Female
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / classification*
  • Killer Cells, Natural / immunology
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Activation
  • Male
  • Receptors, Immunologic / analysis
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, KIR3DL1
  • Receptors, Lymphocyte Homing / analysis


  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • CD56 Antigen
  • Cell Adhesion Molecules
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, KIR3DL1
  • Receptors, Lymphocyte Homing
  • Leukocyte Common Antigens