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-gamma (IFN-gamma) revealed that CD56(bright) cells were those mainly involved in IFN-gamma 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.
BATONI, GIOVANNA (Co-primo) (Corresponding)
ESIN, SEMIH (Co-primo)
|Autori:||Batoni, Giovanna; Esin, Semih; Favilli, Flavia; Pardini, M.; Bottai, Daria; Maisetta, Giuseppantonio; Florio, Walter; Campa, Mario|
|Titolo:||Human CD56bright and CD56dim Natural Killer Cell Subsets Respond Differentially to Direct Stimulation with Mycobacterium bovis Bacillus Calmette-Guérin|
|Anno del prodotto:||2005|
|Digital Object Identifier (DOI):||10.1111/j.1365-3083.2005.01692.x|
|Appare nelle tipologie:||1.1 Articolo in rivista|