[The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells].
OBJECTIVE
To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.


METHODS
The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR.


RESULTS
Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (> 1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1.


CONCLUSIONS
IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.
Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Cai
C
Zhang
Zhi-gang
ZG
Tian
Jian
J
Zhang
Jin-bo
JB
Feng
Jian-hua
JH
Zhang
Xiao-qun
XQ
Xu
D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D054342:Receptors, KIR2DL1; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; C527054:KLRC1 protein, human; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D007371:Interferon-gamma