Gnotobiotic miniature swine for immunobiology and medicine

Abstract

The immune system is a body’s defense system, essential for survival of all vertebrates. It defends not only against invading bacterial, viral, richettsial, fungal and parasitic infections and toxins, and any other intrusions from outsiders, but also provides for surveillance against aberrant endogenous cells which are deviates from normal cells within the host (i.e. cancer), as well as clearing damaged and aging cells, and repairing and maintaining the other tissues. It also has a self-monitoring system for its own defense system to maintain its immunological balance. Over the last 40 years we have been investigating the ontogenic development and regulation of the immune response using the gnotobiotic miniature swine model. We found varying degrees of placental leakage of maternal immunoglobulin in the herds of Minnesota miniature swine and, therefore, constructed a barrier-sustained, specific pathogen-free (SPF)/gnotobiotic miniature swine facility with Hepa-filtered air, sterile water, and sterile feed and maintained under positive pressure. Germ-free (GF) colostrum-deprived piglets obtained by aseptic hysterectomy from Minnesota miniature swine 23 days before term were maintained in GF isolators and associated with normal flora (anaerobic Lactobacillus sp. and anaerobic Streptococcus sp.) and transported into the SPF/gnotobiotic miniature swine facility. We established the breeding and maintenance of SPF/ gnotobiotic miniature swine herds with healthy, nonleaky placental barriers. Thus, gnotobiotic miniature swine are an excellent animal model for immunobiology and medicine. We have demonstrated that: (1) GF colostrumdeprived piglets obtained by aseptic hysterectomy from SPF/gnotobiotic miniature swine are immunologically ‘virgin’ as indicated by the absence of