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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD014358-10
Application #
3312555
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1986-11-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1990-08-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Type
Schools of Medicine
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103
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Steven, W M; Kumar, S N; Stewart, G L et al. (1990) The effects of ethanol consumption on the expression of immunity to Trichinella spiralis in rats. Alcohol Clin Exp Res 14:87-91
Kumar, S N; Stewart, G L; Steven, W M et al. (1990) Role of T cell subsets in the maternal-to-neonatal transmission of immunity against Trichinella spiralis during lactation in rats. J Reprod Immunol 17:69-78
Kumar, S N; Stewart, G L; Steven, W M et al. (1989) Maternal to neonatal transmission of T-cell mediated immunity to Trichinella spiralis during lactation. Immunology 68:87-92
Sontheimer, R D; Matsubara, T; Seelig Jr, L L (1989) A macrophage phenotype for a constitutive, class II antigen-expressing, human dermal perivascular dendritic cell. J Invest Dermatol 93:154-9
Steven, W M; Bulloch, B; Seelig Jr, L L (1989) A morphometric study of the effects of ethanol consumption on lactating mammary glands of rats. Alcohol Clin Exp Res 13:209-12
Kumar, S N; Thomas, B V; Seelig Jr, L L (1988) Immunohistochemical analysis of the stage-specific expression of Ia antigens in the rat mammary gland during pregnancy and lactation. J Reprod Immunol 13:159-73
Tharp, M D; Glass, M J; Seelig Jr, L L (1988) Ultrastructural morphometric analysis of lesional skin: mast cells from patients with systemic and nonsystemic mastocytosis. J Am Acad Dermatol 18:298-306
Tharp, M D; Glass, M J; Seelig Jr, L L (1988) Ultrastructural morphometric analysis of human mast cells in normal skin and pathological cutaneous lesions. J Cutan Pathol 15:78-83
Tharp, M D; Chaker, B; Glass, M J et al. (1987) In vitro functional reactivities of cutaneous mast cells from patients with mastocytosis. J Invest Dermatol 89:264-8

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