This is a proposal to continue studies into the role of local immune regulation in preventing a maternal anti-fetal immune rejection. The underlying rationale is that the system may at times fail, leading to spontaneous abortion. Understanding the mechanisms may be important to decreasing the incidence of such failures. The operating theory is that protection of the developing embryo results from a combination of the immunologically inert physical barrier provided by the trophoblast and a region of local immunosuppression generated in the uterus around the fetus. This environment is generated during the decidual response through a massive increase in numbers of prostaglandin producing cells, principally macrophages. To explore this hypothesis, it is proposed that a study be performed of: 1) Control mechanisms influencing macrophage accumulation in the uterus during pregnancy, 2) Mechanism(s) responsible for immunoregulation by decidual macrophages, 3) The extent and nature of immunoregulation in uterine regional lymph nodes, 4) A model of indomethacin induced abortion which is closely relevant to the proposed immunoregulatory mechanisms. The above specific aims will be studied using a variety of cellular immune techniques in a mouse model system. In conclusion, these studies should lead to an extension of current knowledge of the immunology of pregnancy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017678-07
Application #
3314685
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1983-09-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Burns, T M; Clough, J A; Klein, R M et al. (1993) Developmental regulation of cytokine expression in the mouse brain. Growth Factors 9:253-8
De, M; Sanford, T R; Wood, G W (1993) Expression of interleukin 1, interleukin 6 and tumour necrosis factor alpha in mouse uterus during the peri-implantation period of pregnancy. J Reprod Fertil 97:83-9
De, M; Sanford, T; Wood, G W (1993) Relationship between macrophage colony-stimulating factor production by uterine epithelial cells and accumulation and distribution of macrophages in the uterus of pregnant mice. J Leukoc Biol 53:240-8
Choudhuri, R; Wood, G W (1993) Production of interleukin-1, interleukin-6, and tumor necrosis factor alpha in the uterus of pseudopregnant mice. Biol Reprod 49:596-603
De, M; Sanford, T H; Wood, G W (1992) Detection of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in the uterus during the second half of pregnancy in the mouse. Endocrinology 131:14-20
De, M; Sanford, T R; Wood, G W (1992) Interleukin-1, interleukin-6, and tumor necrosis factor alpha are produced in the mouse uterus during the estrous cycle and are induced by estrogen and progesterone. Dev Biol 151:297-305
Wood, G W; De, M; Sanford, T et al. (1992) Macrophage colony stimulating factor controls macrophage recruitment to the cycling mouse uterus. Dev Biol 152:336-43
Wood, G W; Greenwood, J H (1991) Murine CD4-CD8- thymocytes are stimulated by interleukin-2 to proliferate in vitro in chemically defined medium. Thymus 18:15-31
De, M; Wood, G W (1991) Analysis of the number and distribution of macrophages, lymphocytes, and granulocytes in the mouse uterus from implantation through parturition. J Leukoc Biol 50:381-92
De, M; Choudhuri, R; Wood, G W (1991) Determination of the number and distribution of macrophages, lymphocytes, and granulocytes in the mouse uterus from mating through implantation. J Leukoc Biol 50:252-62

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