Lymphocyte migration and differentiation in a large-animal model: the sheep

The size and docility of the sheep permit various surgical interventions and repeated collections of biological samples. Development of lymphatic cannulation techniques in this species enabled the investigation of the kinetics of lymphocyte migration in single lymph nodes of not only postnatal animals but also of fetuses at various stages of gestation. It was first demonstrated in the sheep that lymphocyte recirculation commences in the fetus without any exogenous antigenic stimulus. Using these cannulation techniques, it is also possible to investigate humoral events such as the secretion of lymphokines taking place in single lymph nodes with regard to the regulation of lymphopoiesis and the immune response. An extracorporeal perfusion system has been used successfully to investigate the emigration of cells from various lymphoid organs in the sheep. This apparatus enables cells to be labelled in their normal microenvironment with radioisotopes and/or fluorescent probes without destroying the normal tissue architecture. In studies with outbred animals such as the sheep, an investigation in which an individual animal is studied as a case history over a long time often provides much more information than studies based on single-point examinations of many animals and is much closer to the clinical study of immunological problems in individual humans. The recent development of an array of monoclonal antibodies against lymphocyte surface antigens in sheep will help to further dissect the complexity of immunological phenomena. Therefore, the sheep is a useful animal model to study physiological events taking place in the lymphoid system, and in vivo studies in this species will continue to offer a great potential for research of biological relevance and supplement the research done on the in vitro manipulation of cells and biological products related to the immune system.