The major objective of this proposed research is to characterize and document the transmission of circulating lymphocytes into maternal mammary exosecretions and the fate of ingested cells within the neonate. Using inbred rat strains, we plan to show by adoptive transfer of radiolabeled cells and subsequent autoradiography that specific subpopulations of maternal lymphocytes migrate into the mammary gland and then the milk of lactating females. The possible genetic control of this process by regions of the major histocompatibility complex will also be investigated. The ability of cells to survive in the gastrointestinal tract and transit the gut epithelium will be documented by 1) graft-versus-host reactivity of parental lymphocytes placed into isolated ileal segments in F1 hybrid adults, measured by draining node enlargement and local damage, as well as autoradiographic analysis after similar injections of radiolabeled cells; 2) tracing lymphocytes fed to rat neonates by autoradiographic analysis of neonatal tissues after feeding radiolabeled cells and by immunofluorescence to detect cells within neonatal tissues bearing maternal markers; and 3) a previously determined model system of intestinal lymphoid tissue development in the neonatal rat to establish, on a morphological basis, alterations in this development due to the introduction of parental or other allogeneic lymphocytes into the gastrointestinal tract of F1 hybrid neonates. The role of Peyer's patches in the transepithelial migration of lymphocytes will be studied in both the adult and neonatal systems. Additionally, the capacity of cells isolated from milk to transit both the adult and neonatal gut epithelium will be investigated. Electron microscopy will be utilized in all experiments to assess the morphology of cells crossing the various epithelia and elucidate their mechanism of transit. A thorough understanding of the role of lymphocytes in milk and their capacity to seed the lymphoid tissue of the neonate could provide new means of disease control and prevention during the neonatal period.
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