|POWELL, ELLIS - Iowa State University|
|CUNNICK, JOAN - Iowa State University|
|KNETTER, SUSAN - Iowa State University|
|WAIDE, EMILY - Iowa State University|
|DEKKERS, JACK - Iowa State University|
|TUGGLE, CHRISTOPHER - Iowa State University|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2016
Publication Date: 4/19/2016
Citation: Powell, E.J., Cunnick, J.E., Knetter, S.M., Loving, C.L., Waide, E.H., Dekkers, J.C., Tuggle, C. 2016. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene. Veterinary Immunology and Immunopathology. 175:1-6. doi: 10.1016/j.vetimm.2016.04.008.
Interpretive Summary: A Severe Combined Immunodeficiency (SCID) line of pigs has been identified, and is a useful model to understand the role of the immune system in health and disease. The SCID pig model with a mutation in a specific gene (Artemis) has one particular type of immune cell, though other types do not develop and are not present in the animal. It is important to evaluate the function of the immune cells present in the Artemis SCID model, and work shown here indicates that the immune cells referred to as Natural Killer (NK) cells respond to stimulation like NK cells from normal pigs. NK cells from both normal and SCID pigs are able to kill tumor cells and produce a compound (perforin) following stimulation with immune signaling compounds (cytokines).
Technical Abstract: 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 cells from all three lines. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from either SCID or non-SCID pigs after IL-2 cytokine treatment. While NK cells constituted an average of 27 percent of the peripheral blood mononuclear cell population in SCID pigs, compared to only 4 percent in non-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.