Exit of recirculating lymphocytes from lymph nodes is directed by specific exit signals.
During recirculation, lymphocytes leave the peculiar structurally inverted lymph nodes (LN) of pigs via blood vessels instead of via efferent lymphatics, as in sheep and other mammals. This functional difference provided an opportunity to show the existence of signals directing lymphocyte exit from LN. The recirculation of pig peripheral blood lymphocytes was traced through fetal sheep LN and of sheep PBL into and out of unsuckled newborn piglet LN, using the lack of natural antibody or natural killer cell function in these immunologically mature young to compare foreign and homologous lymphocyte behavior. In spite of some 50 million years of evolutionary divergence, the detailed kinetics and route of recirculation of the xenogeneic PBL were essentially the same as those of the host species. Thus determinants guiding the anomalous blood exit from pig LN must involve conserved "exit" signals in a new site and not changes in pig lymphocyte homing receptors.