Abstract

The specific aims of this research are to examine the receptors, ligands, and functions of human decidual lymphocytes with a view to understanding their possible roles in implantation and pregnancy. In particular, we wish: 1. To examine the biochemistry and possible functions of novel proteins overexpressed by human decidual natural killer (NK) cells that may be involved in down-modulation of the immune response, to continue analysis of the transcriptional profiles of these cells and to study their cytoxicity and ability to secrete cytokines. 2. To assess the role of invariant NKT (iNKT) cells in the decidua by studying their interaction with CD1d expressed on several cell types, by examining the relation of their Vbeta repertoire to cytokine secretion, by testing the hypothesis that they function to regulate the immune response at the maternal-fetal interface and by examining their complete transcriptional profiles. 3. To examine the expression in the placenta of putative Class I MHC protein ligands for decidual NK and iNKT cells and of the GM-CSF receptor and to examine the interaction of placental extravillous cytotrophoblasts with NK and iNKT cells and with GM-CSF.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI053330-01A1
Application #
6685460
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Macchiarini, Francesca
Project Start
2003-06-15
Project End
2007-11-30
Budget Start
2003-06-15
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$208,560
Indirect Cost

  Institution

Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

van der Zwan, Anita; Bi, Kevin; Norwitz, Errol R et al. (2018) Mixed signature of activation and dysfunction allows human decidual CD8+ T cells to provide both tolerance and immunity. Proc Natl Acad Sci U S A 115:385-390
Allan, David S J; Cerdeira, Ana Sofia; Ranjan, Anuisa et al. (2017) Transcriptome analysis reveals similarities between human blood CD3- CD56bright cells and mouse CD127+ innate lymphoid cells. Sci Rep 7:3501
Crespo, Ângela C; van der Zwan, Anita; Ramalho-Santos, João et al. (2017) Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections. J Reprod Immunol 119:85-90
Crespo, Ângela C; Strominger, Jack L; Tilburgs, Tamara (2016) Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection. Proc Natl Acad Sci U S A 113:15072-15077
Ferreira, Leonardo M R; Meissner, Torsten B; Mikkelsen, Tarjei S et al. (2016) A distant trophoblast-specific enhancer controls HLA-G expression at the maternal-fetal interface. Proc Natl Acad Sci U S A 113:5364-9
Tilburgs, Tamara; Evans, J Henry; Crespo, Ângela C et al. (2015) The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface. Proc Natl Acad Sci U S A 112:13312-7
Tilburgs, Tamara; Crespo, Ângela C; van der Zwan, Anita et al. (2015) Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes. Proc Natl Acad Sci U S A 112:7219-24
Guerin, Leigh; Wu, Vernon; Houser, Brandy et al. (2015) CD1 Antigen Presentation and Autoreactivity in the Pregnant Human Uterus. Am J Reprod Immunol 74:126-35
Tilburgs, Tamara; Strominger, Jack L (2013) CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity. Am J Reprod Immunol 69:395-407
Chen, Ting; Darrasse-Jèze, Guillaume; Bergot, Anne-Sophie et al. (2013) Self-specific memory regulatory T cells protect embryos at implantation in mice. J Immunol 191:2273-81

Showing the most recent 10 out of 13 publications