Multiple deficiencies underlie NK cell inactivity in lymphotoxin-alpha gene-targeted mice.
We have evaluated the NK cell antitumor activity in lymphotoxin (LT)-deficient mice. Both NK cell-mediated tumor rejection and protection from experimental metastases were significantly compromised in LT-alpha-deficient mice. Analysis of LT-alpha-deficient mice revealed that the absolute number of alphabetaTCR- NK1.1+ NK cells was reduced in bone marrow and thymus, but with overall proportional decreases in other hemopoietic organs. In addition, the antitumor potential of alphabetaTCR- NK1.1+ cells, as determined by their lytic capacity and perforin expression, was reduced 1.5- to 3-fold in LT-alpha-deficient mice, as compared with wild-type mice. Combined defects in NK cell development and effector function contribute to compromised NK cell antitumor function in LT-alpha-deficient mice.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia. m.smyth@ari.unimelb.edu.au
Johnstone
R W
RW
Cretney
E
E
Haynes
N M
NM
Sedgwick
J D
JD
Korner
H
H
Poulton
L D
LD
Baxter
A G
AG
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D018390:Gene Targeting; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008233:Lymphotoxin-alpha / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D008233:Lymphotoxin-alpha