A shift toward inhibitory receptors and impaired effector functions on NK cells contribute to immunosuppression during sepsis.

In this study, we aimed to decipher NK cell immunity of septic patients in a more comprehensive way. We found that cytotoxicity of NK cells dramatically decreased during sepsis, likely due to the reduction of cluster of differentiation (CD)3- CD56+ NK cells and a shift of phenotypic changes of NK group 2 member (NKG2) receptors, natural cytotoxicity receptors (NCRs) and killer immunoglobulin-like receptors (KIRs) toward inhibitory receptors demonstrated by CD3- CD56+ NK cells in septic patients. Expression of the activation indicator CD69 and cytotoxic associated marker CD107a on CD3- CD56+ NK cells in healthy adults was significantly lower than that of septic patients. Although perforin and granzyme B on CD3- CD56+ NK cells from all groups exhibited equivalently high levels, CD3- CD56+ NK cells from septic patients exhibited a much lower fold increase of CD69 and CD107a compared with healthy adults after coculturing with K562 cells in vitro. Cytokine production of IFN-γ and TNF-α on CD3- CD56+ NK cells in septic patients was also impaired after stimulation by PMA and ionomycin. We found that the proportion of NK cells in lymphocytes was negatively associated with patient 28 d death in septic patients. Phenotypic changes of a shift toward inhibitory receptors and impairment of effector functions of NK cells might be an important mechanism of immunosuppression during sepsis.
PMID: 31385383 [PubMed - as supplied by publisher]

Source: Journal of Leukocyte Biology - August 5, 2019 Category: Hematology Authors: Feng T, Liao X, Yang X, Yang C, Lin F, Guo Y, Kang Y, Li H Tags: J Leukoc Biol Source Type: research