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Human CD56 bright and CD56 dim Natural Killer Cell Subsets Respond Differentially to Direct Stimulation with Mycobacterium bovis Bacillus Calmette‐Guérin
Author(s) -
Batoni G.,
Esin S.,
Favilli F.,
Pardini M.,
Bottai D.,
Maisetta G.,
Florio W.,
Campa M.
Publication year - 2005
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2005.01692.x
Subject(s) - perforin , cytotoxic t cell , biology , lymphokine activated killer cell , interleukin 12 , granzyme , interleukin 21 , granzyme b , natural killer cell , immunology , microbiology and biotechnology , t cell , immune system , in vitro , biochemistry
Mycobacterium bovis bacillus Calmette‐Guérin (BCG) is capable of directly stimulating several effector functions of human natural killer (NK) cells in the absence of interleukin‐12 and professional antigen presenting cells. To assess the contribution of two main human NK‐cell subsets (CD56 dim and CD56 bright ) to the overall in vitro NK‐cell response to BCG, peripheral blood mononuclear cells depleted of nylon wool‐adherent cells or purified NK cells were stimulated with live BCG. By combining intranuclear bromodeoxyuridine (BrdU) staining and analysis of CD56 marker intensity, statistically higher percentages of BrdU + cells were found among the CD56 bright subset than the CD56 dim subset after 6 days of stimulation with BCG. Similarly, evaluation of intracellular interferon‐γ (IFN‐γ) revealed that CD56 bright cells were those mainly involved in IFN‐γ production in response to BCG. In contrast, the CD56 dim subset contained higher levels of perforin and granzyme A, two key molecules for exocytosis‐mediated cytotoxicity, than the CD56 bright subset. Although 16–20‐h stimulation with BCG did not substantially alter the expression of cytotoxic molecules by the two subsets, a decrease in perforin content was observed in the CD56 dim , but not in the CD56 bright subset, following 4‐h incubation with the NK‐sensitive target K562 cell line. This decrease in perforin content correlated with the induction by BCG‐stimulated NK cells, of early markers of apoptosis on target cells to a greater extent than unstimulated cells suggesting a major role for the CD56 dim subset in cytotoxic activity in response to BCG. Taken together, these results demonstrate that CD56 bright and CD56 dim human NK‐cell subsets exert different functional activities in response to a live bacterial pathogen.