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IFN‐γ Production and Degranulation are Differentially Regulated in Response to Stimulation in Murine Natural Killer Cells
Author(s) -
Vahlne G.,
Becker S.,
Brodin P.,
Johansson M. H.
Publication year - 2008
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.1365-3083.2007.02026.x
Subject(s) - degranulation , nkg2d , interleukin 21 , microbiology and biotechnology , interleukin 12 , lymphokine activated killer cell , biology , stimulation , chemistry , immunology , receptor , cytotoxic t cell , t cell , immune system , in vitro , biochemistry , endocrinology
Activation of natural killer (NK) cells is induced via receptors like NKG2D, NKR‐P1C and NKp46. This activation is balanced by interactions with inhibitory receptors. NK cell activation can lead to cytotoxicity mediated via polarized exocytosis of secretory lysosomes (degranulation) and interferon (IFN)‐γ production. We studied cell surface mobilization of a molecule present in secretory lysosomes, CD107a (LAMP‐1), to monitor the relationship between degranulation of NK cells and their production of IFN‐γ at the single cell level. A comparison of responses in naive mouse NK cells and NK cells pre‐activated with the type I interferon‐inducer tilorone demonstrated a dramatic influence of pre‐activation, allowing potent degranulation and IFN‐γ responses to NKG2D mediated stimulation that were not observed with naive NK cells. Degranulation and IFN‐γ production were performed by overlapping NK cell populations with generally higher frequencies of degranulating than IFN‐γ producing NK cells. An NK cell subset analysis based on expression of Mac‐1 and CD27 revealed that immature NK cells (Mac‐1 lo CD27 hi ) are preferentially degranulating, Mac‐1 hi CD27 hi cells perform both effector functions efficiently, while the most mature (Mac‐1 hi CD27 lo ) NK cells display reduced degranulation but with maintained IFN‐γ production.