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- Title
Human CD56<sup>bright</sup> and CD56<sup>dim</sup> Natural Killer Cell Subsets Respond Differentially to Direct Stimulation with Mycobacterium bovis Bacillus Calmette-Guérin.
- Authors
Batoni, G.; Esin, S.; Favilli, F.; Pardini, M.; Bottai, D.; Maisetta, G.; Florio, W.; Campa, M.
- Abstract
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 (CD56dim and CD56bright) 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 CD56bright subset than the CD56dim subset after 6 days of stimulation with BCG. Similarly, evaluation of intracellular interferon-γ (IFN-γ) revealed that CD56bright cells were those mainly involved in IFN-γ production in response to BCG. In contrast, the CD56dim subset contained higher levels of perforin and granzyme A, two key molecules for exocytosis-mediated cytotoxicity, than the CD56bright 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 CD56dim, but not in the CD56bright 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 CD56dim subset in cytotoxic activity in response to BCG. Taken together, these results demonstrate that CD56bright and CD56dim human NK-cell subsets exert different functional activities in response to a live bacterial pathogen.
- Subjects
BCG vaccines; BACTERIAL vaccines; BACILLUS (Bacteria); MYCOBACTERIUM; KILLER cells; ANTIBODY-dependent cell cytotoxicity; IMMUNOLOGY
- Publication
Scandinavian Journal of Immunology, 2005, Vol 62, Issue 6, p498
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.1365-3083.2005.01692.x