Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 35, Issue 9, Pages 2608-2616Publisher
WILEY
DOI: 10.1002/eji.200526122
Keywords
granzyme; perforin; cytotoxic T lymphocytes; natural killer cell; memory T cell
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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(+)/CCR5(high)/CCR7(-)/Perforin-/(low)/IFN-gamma(+) memory-like phenotype, while all CD56(bright) NK cells were also positive for GrK. In addition, GrK was also expressed in subpopulations of CD56(+) T cells, CD4(+) T cells, and TCR gamma delta(+) T cells. In contrast, GrB was primarily expressed in CD56(dim) NK cells and differentiated memory CD8(+) T cells with the CD27(-/low)/CD28(-/low)/CCR5(-/low)/CCR7(-)/ CD11b(+)/perforin(high) 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(-).
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