m144, a murine cytomegalovirus (MCMV)-encoded major histocompatibility complex class I homologue, confers tumor resistance to natural killer cell-mediated rejection.
Until now, it has been unclear whether murine cytomegalovirus (MCMV)-encoded protein m144 directly regulates natural killer (NK) cell effector function and whether the effects of m144 are only strictly evident in the context of MCMV infection. We have generated clones of the transporter associated with antigen processing (TAP)-2-deficient RMA-S T lymphoma cell line and its parent cell line, RMA, that stably express significant and equivalent levels of m144. In vivo NK cell-mediated rejection of RMA-S-m144 lymphomas was reduced compared with rejection of parental or mock-transfected RMA-S clones, indicating the ability of m144 to regulate NK cell-mediated responses in vivo. Significantly, the accumulation of NK cells in the peritoneum was reduced in mice challenged with RMA-S-m144, as was the lytic activity of NK cells recovered from the peritoneum. Expression of m144 on RMA-S cells also conferred resistance to cytotoxicity mediated in vitro by interleukin 2-activated adherent spleen NK cells. In summary, the data demonstrate that m144 confers some protection from NK cell effector function mediated in the absence of target cell class I expression, but that in vivo the major effect of m144 is to regulate NK cell accumulation and activation at the site of immune challenge.
Cretney
E
E
Cellular Immunity Laboratory, The Austin Research Institute, Melbourne, Victoria, Australia.
Degli-Esposti
M A
MA
Densley
E H
EH
Farrell
H E
HE
Davis-Poynter
N J
NJ
Smyth
M J
MJ
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D009368:Neoplasm Transplantation; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; C105297:m144 protein, Mouse cytomegalovirus 1