NK cells modulate MHC class I expression on tumor cells and their susceptibility to lysis.
Cytotoxicity and production of cytokines are two important functions of NK cells. These two different NK functions were studied in a syngeneic rat model in relation to MHC class I expression. We focussed on the mechanism by which NK cells modulate MHC class I expression on target cells and how this interferes with NK cell-mediated lysis. Using transfection experiments an inhibitory role on NK cell cytotoxicity for expression of target cells of RT1.A, rat MHC class I, was found. Co-culturing syngeneic tumor cells and NK cells resulted in enhanced MHC class I expression on the surviving tumor cell fraction, which was less susceptible to NK lysis. Increased tumor cell MHC class I was due to production of a soluble factor by NK cells, most likely interferon gamma. The regulatory function of NK cells shows here, that the enhancing of MHC class I expression on tumor cells in vitro and in vivo, results in downregulation of their target cell killing, but at the same time may facilitate the cytotoxic T cell function.
Jonges
L E
LE
Department of Pathology, Leiden University Medical Center, The Netherlands. ljonges@pat.azl.nl
Giezeman-Smits
K M
KM
van Vlierberghe
R L
RL
Ensink
N G
NG
Hagenaars
M
M
Joly
E
E
Eggermont
A M
AM
van de Velde
C J
CJ
Fleuren
G J
GJ
Kuppen
P J
PJ
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C038353:histocompatibility antigens RT, rat; D007371:Interferon-gamma