Characterizing the Iowa State University Severe Combined Immune Deficient (SCID) Pig

We previously identified a line of SCID pigs caused by mutations in the Artemis gene, that contain NK but not B or T cells. These SCID pigs cannot prevent human xenograft survival, and may be useful for biomedical research, yet need further characterization. We investigated the function of SCID NK cells, as a major role for NK cells is removal of foreign cells. We found porcine NK cells can kill in vitro the human cancer cells that survived in vivo, and that NK cells from SCID pigs can kill human K562 cells. Thus xenograft survival in SCID pigs is not due to an intrinsic NK cell deficit. We then tested whether innate immunity alone can control IAV infection. SCID/normal piglets were inoculated with IAV or PBS (n=5-8 animals/treatment). Viral titers in nasal secretions (NS) were similar between groups on 1, 3 and 5 days post-infection (dpi), but at 7dpi SCID pigs had much higher virus in NS and bronchial-alveolar lavage fluid (BALF) yet had significantly less lung microscopic pathology. Interferon-alpha, interferon-gamma, IL-1beta and IL-6 in BALF were elevated in IAV-SCID pigs, indicating an innate immune response had occurred. Thus the lack of T and B cells in SCID pigs resulted in inability to control viral replication, indicating that IAV clearance requires the adaptive immune system. Finally, we have shown that administration of an immunoglobulin preparation from slaughterhouse blood increases serum immunoglobulin levels in SCID pigs post-weaning and may be a useful palliative treatment to maintain SCID pigs for longer-term studies.