The overall goal of this research is to understand the mechanisms of maternal immune tolerance to the allogeneic fetus in pregnancy. The intimacy between the maternal immune system and the fetal allograft is an unparalleled physiological situation in which paternally inherited fetal antigens expressed by the fetus are unfailingly tolerated in normal pregnancy. The studies proposed herein further investigate previous observations that both murine and human pregnancy results in highly specific recognition of paternally- inherited fetal alloantigens. This holds true for both major and minor histocompatibility antigens. In this proposal, we will employ a murine model of a transgenic fetal minor histocompatibility antigen in combination with maternal CD4+ and CD8+ lymphocytes that specifically react to this antigen to investigate maternal lymphocyte responses and induction of tolerance to fetal antigen. We also investigate the expression, timing and presentation of fetal minor histocompatibility antigens in the human placenta.
Our Specific Aims are: 1. Determine the phenotypic and functional properties of mHAg-specific T cells generated during murine pregnancy. 2. Determine the phenotypic and functional properties of antigen presenting cells displaying fetal antigen to T cells during pregnancy. 3. Investigate the expression and functional significance of fetally-derived mHAg in human pregnancy. Collectively, these studies will yield important new insights into the responses of maternal lymphocytes to fetal antigen that lead to immunological adaptation and harmonious coexistence of mother and fetus. This knowledge could in turn, give new light into the pathogenesis of pregnancy failure, and proved a basis for the development of therapeutic agents, not only co combat infertility, but also cancer, autoimmune disease and transplant rejection.

Public Health Relevance

Numerous medical situations arise from either inappropriate immune tolerance to antigen, such as cancer, or inappropriate immune intolerance to antigen, such as failed pregnancy, autoimmune disease, and transplantation rejection. Pregnancy represents a perfect balance of coexistence between a foreign "graft" and the maternal immune system that has adapted to promote the growth of the fetus rather than reject it. Understanding the events surrounding this unique physiological situation will yield insight on how infertility, cancer and autoimmune disease may be alleviated.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Pregnancy and Neonatology Study Section (PN)
Program Officer
Ilekis, John V
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University of Kansas
Anatomy/Cell Biology
Schools of Medicine
Kansas City
United States
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Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K et al. (2014) Ovarian autoimmune disease: clinical concepts and animal models. Cell Mol Immunol 11:510-21
Perchellet, Antoine L; Jasti, Susmita; Petroff, Margaret G (2013) Maternal CD4ýýý and CD8ýýý T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice. Biol Reprod 89:102
Ma, Kimberly K; Petroff, Margaret G; Coscia, Lisa A et al. (2013) Complex chimerism: pregnancy after solid organ transplantation. Chimerism 4:71-7
Holland, Olivia J; Linscheid, Caitlin; Hodes, Herbert C et al. (2012) Minor histocompatibility antigens are expressed in syncytiotrophoblast and trophoblast debris: implications for maternal alloreactivity to the fetus. Am J Pathol 180:256-66
Taglauer, Elizabeth S; Adams Waldorf, Kristina M; Petroff, Margaret G (2010) The hidden maternal-fetal interface: events involving the lymphoid organs in maternal-fetal tolerance. Int J Dev Biol 54:421-30
Petroff, Margaret G; Perchellet, Antoine (2010) B7 family molecules as regulators of the maternal immune system in pregnancy. Am J Reprod Immunol 63:506-19
Taglauer, Elizabeth S; Yankee, Thomas M; Petroff, Margaret G (2009) Maternal PD-1 regulates accumulation of fetal antigen-specific CD8+ T cells in pregnancy. J Reprod Immunol 80:12-21
Holets, L M; Carletti, M Z; Kshirsagar, S K et al. (2009) Differentiation-induced post-transcriptional control of B7-H1 in human trophoblast cells. Placenta 30:48-55
Taglauer, Elizabeth S; Trikhacheva, Ann S; Slusser, Joyce G et al. (2008) Expression and function of PDCD1 at the human maternal-fetal interface. Biol Reprod 79:562-9
Petroff, Margaret G; Phillips, Teresa A; Ka, Hakhyun et al. (2006) Isolation and culture of term human trophoblast cells. Methods Mol Med 121:203-17

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