One of the major questions in maternal-neonatal immunologic relationships has been the role of maternally derived immunity delivered via milk in the early protection of the neonate. The long term goals of this research are directed towards an understanding of the factors in the mother and child responsible for the accmulation, transmission and neonatal uptake of immune cells, especially during antigenic exposure. Using our model systems established for assessng the baby's gastrointestinal immune development and for artifically feeding newborn rats, and the techniques of autoradiography, indirect immunofluorescence, electron microscopy and 3-dimensional computer assisted reconstructions, we propose to show that: (1) T-lymphocytes obtained from various tissue sources and milk, when fed to neonates, are able to transmit their gastric epithelium, (2) this cellular uptake produces a functional transfer of cell-mediated immunity to the baby, and (3) increased pasage of immune cells into the baby's tissues can be effected by alterations in the development of its gastrointestinal immune system. In addition, various aspects of mammary gland accumulation of T-cells during pregnancy and lactation will be investigated. These include: (1) the distribution of various subsets of T-cells in the mammary gland and milk and (2) studies of the signal(s) by which T-lymphocytes are attracted to the mammary gland during pregnancy and lactation. A number of highly specific T-cell subset markers are now available and will allow a better characterization of the infiltration of cells into the mammary gland and milk. The appearance of Ia antigens in the mammary gland and neonatal intestinal tract will be assessed using the monoclonal antibodies that recognize the rat antigens homologous to the gene products of the I-A and I-E subregions of the mouse MHC. Manipulations to elicit enhanced epithelial is expression and cell-mediated immune functions in the mother and child, like induction of GVHD, parasitic infection and contact sensitivity to TNP, will be used to elucidate the underlying mechanisms of cell selection, recruitment and transfer during lactation. 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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