The role of MHC class I expression in rat NK cell-mediated lysis of syngeneic tumor cells and virus-infected cells.
In this study the role of MHC class I antigen expression in rat natural killer (NK) cell-mediated lysis was investigated. Various rat tumor cell lines and two Adenovirus (Ad)-transformed rat cell lines were tested for their expression levels of total MHC class I and two MHC class I alleles, RT1.A and RT1.C, by flow cytometry. Their susceptibility to NK cell-mediated lysis in relation to MHC class I expression was determined by 51Cr release assays. IFN-gamma is know to increase the expression of MHC class I. Therefore target cell with and without prior IFN-gamma treatment were examined for MHC class I expression and its effect on NK lysis. An significant inverse exponential relationship was found. To investigate the effect of virus infection on MHC class I expression and target cell lysis by NK cells, rat embryonal fibroblasts (REF) were infected with cytomegalovirus (CMV) and used as target cells for NK cell-mediated lysis. Results showed that these virus-infected cells were less susceptible to NK lysis than non-infected cells. Moreover, the non-infected cells expressed less MHC class I than the infected cells, indicating that also in this case, there was an inverse correlation between MHC class I expression and susceptibility to lysis by NK cells. Subsequently, we showed that sorted subsets of predominantly CD8-positive and CD8-negative NK cells lysed a MHC class I-positive tumor cell line at the same level. This suggests that CD8 is not likely to participate as a receptor for MHC class I in NK cell-mediated lysis in a syngeneic rat model.
Giezeman-Smits
K M
KM
Department of Pathology, University of Leiden, The Netherlands.
Kuppen
P J
PJ
Ensink
N G
NG
Eggermont
A M
AM
Stals
F
F
Wonigeit
K
K
Fleuren
G J
GJ
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I