Human natural killer (NK) cells produce immunoregulatory cytokines in response to stimulation with monocyte-derived cytokines (monokines). These NK-derived cytokines (e.g. IFN-γ, GM-CSF) are important for the host's early defense against a variety of bacterial, viral, and parasitic pathogens. Human NK cell subsets can be distinguished by CD56 surface density expression (e.g. CD56bright and CD56dim). In this study we have investigated cytokine production by NK cell subsets in response to stimulation with recombinant monokines or phorbol esters (PMA) and ionomycin. CD56bright NK cells produced significantly greater levels of IFN-γ, TNF-β, GM-CSF, TNF-α, IL-10, and IL13 protein than CD56dim NK cells. Furthermore, CD56bright NK cells co-cultured with LPS-activated macrophages (an endogenous source of monokines) produced significantly more cytokines than the CD56dlm NK cell subset. Therefore, we present novel evidence showing that CD56bright NK cells are the primary source of NK cell-derived immunoregulatory cytokines. These data support a model whereby CD56bright and CD56dim NK cells represent functionally distinct subsets of mature human NK cells. Knowledge of the differential functional attributes of CD56bright (e.g. immunoregulatory cytokine production) and CD56dim (e.g. cytotoxicity) subsets may enable us to design strategies that preferentially activate that subset with the greatest therapeutic potential for a particular disease.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology