Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood

Eur J Immunol. 2005 Sep;35(9):2608-16. doi: 10.1002/eji.200526122.


NK cells and cytotoxic T lymphocytes can induce apoptosis in virus-infected and transformed target cells via the granule exocytosis pathway. The key components of the cytolytic granules are perforin and several serine esterases, termed granzymes. While the cellular distribution of human granzymes A (GrA) and B (GrB) has been well characterized much less is known about the expression pattern of human granzyme K (GrK). In this study GrA, GrB, and GrK expression was analyzed in human peripheral blood lymphocytes using flow cytometry. There was a distinct population of GrK expressing CD8+ T cells with a CD27+/CD28+/CCR5high/CCR7-/perforin-/low/IFN-gamma+ memory-like phenotype, while all CD56bright NK cells were also positive for GrK. In addition, GrK was also expressed in subpopulations of CD56+ T cells, CD4+ T cells, and TCRgammadelta+ T cells. In contrast, GrB was primarily expressed in CD56dim NK cells and differentiated memory CD8+ T cells with the CD27-/low/CD28-/low/CCR5-/low/CCR7-/CD11b+/perforinhigh phenotype. Only few CD8+ T cells expressed both GrB and GrK. GrA was found to be co-expressed in all GrB- and GrK-expressing T cells. Our findings suggest that granzyme expression during the differentiation process of memory CD8+ T cells might be as follows: GrA+/GrB-/GrK+ --> GrA+/GrB+/GrK+ --> GrA+/GrB+/GrK-.

MeSH terms

  • CD11b Antigen / biosynthesis
  • CD11b Antigen / genetics
  • CD11b Antigen / immunology
  • CD28 Antigens / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / immunology
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Granzymes
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / enzymology*
  • Killer Cells, Natural / immunology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, CCR5 / immunology
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology*
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology


  • CD11b Antigen
  • CD28 Antigens
  • Cytokines
  • HLA-DR Antigens
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Receptors, CCR5
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Perforin
  • GZMB protein, human
  • GZMK protein, human
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human