The mammalian fetus in an outbred population invariably expresses antigens, some of them histocompatability antigens which are derived from both parents. If those antigens were expressed by allografts of other tissue, the grafts would be rejected, yet the fetus develops with few complications within the uterine environment. Obviously this is an immunologic enigma. A general theory has evolved which suggests that one reason for survival of the fetal allograft is the development of local immunoregulation. The rationale for the present proposal is that tissues surrounding the fetus, the uterus, placenta and yolk sac, contain suppressor cells which prevent rejection of fetal tissue. The research described herein is designed to localize, identify and quantify immunologic cells (lymphocytes, macrophages and granulocytes) within tissue that surrounds the fetus, i.e., the uterus, placenta and yolk sac. It is then designed to determine the degree of suppressor cell activity for T-lymphocyte mediated cell function, determine the nature of the suppressor cells and begin to understand by what mechanism the suppressor cells act to modulate lymphocyte function. Finally experiments will be performed to evaluate the effect on pregnancy of agents which block the activity of the putative suppressor cells. These series of experiments should allow us to determine 1) if immunoregulation occurs and is important in promoting fetal survival and 2) what cells are responsible for immunoregulation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017678-03
Application #
3314682
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1983-09-01
Project End
1987-03-31
Budget Start
1985-09-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1985
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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