NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene.
We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor cell lines, PANC-1 and A375-SM, survived after injection into these SCID pigs, but, as we demonstrate here, these cells, as well as K562 tumor cells, can be lysed in vitro by NK cells from SCID and non-SCID pigs. NK cells from both SCID and non-SCID pigs required activation in vitro with either recombinant human IL-2 or the combination of recombinant porcine IL-12 and IL-18 to kill tumor targets. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment. While CD16+, CD172- NK cells constituted an average of only 4% in non-SCID pigs, NK cells averaged 27% of the peripheral blood mononuclear cell population in SCID pigs. We found no significant differences in killing activity per NK cell between SCID and non-SCID pigs. We conclude that survival of human cancer cells in these SCID pigs is not due to an intrinsic defect in NK cell killing ability.
Iowa State University, Department of Animal Science, Ames, IA, USA.
Ellis J
EJ
Powell
Iowa State University, Department of Animal Science, Ames, IA, USA.
Joan E
JE
Cunnick
Iowa State University, Department of Animal Science, Ames, IA, USA.
Susan M
SM
Knetter
USDA-ARS-National Animal Disease Center, Food Safety and Enteric Pathogens Research Unit, USA.
Crystal L
CL
Loving
Iowa State University, Department of Animal Science, Ames, IA, USA.
Emily H
EH
Waide
Iowa State University, Department of Animal Science, Ames, IA, USA.
Jack C M
JC
Dekkers
Iowa State University, Department of Animal Science, Ames, IA, USA. Electronic address: cktuggle@iastate.edu.
Christopher K
CK
Tuggle
D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D009368:Neoplasm Transplantation; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology*; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000276:immunology*; D014183:Transplantation, Heterologous
D004720:Endonucleases
Artemis; Innate immunity; NK cells; Natural killer; Perforin; Pig; SCID