Isolator and other neonatal piglet models in developmental immunology and identification of virulence factors*

Abstract The postnatal period is a ‘critical window’, a time when innate and passive immunity protect the newborn mammal while its own adaptive immune system is developing. Neonatal piglets, especially those reared in isolators, provide valuable tools for studying immunological development during this period, since environmental factors that cause ambiguity in studies with conventional animals are controlled by the experimenter. However, these models have limited value unless the swine immune system is first characterized and the necessary immunological reagents developed. Characterization has revealed numerous features of the swine immune system that did not fit mouse paradigms but may be more generally true for most mammals. These include fetal class switch recombination that is uncoupled from somatic hypermutation, the relative importance of the molecular mechanisms used to develop the antibody repertoire, the role of gut lymphoid tissue in that process, and the limited heavy chain repertoire but diverse IgG subclass repertoire. Knowledge gained from studies of adaptive immunity in isolator-reared neonatal pigs suggests that isolator piglets can be valuable in identification of virulence factors that are often masked in studies using conventional animals.