EXCEED THE SPACE PROVIDED.
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.' . 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. . To assess the role of invariant NKT (iNKT) cells in the decidua by studying their interaction with CDld expressed on several cell types, by examining the relation of their V_ 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. . 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. =ERFORMANCE SITE(S) (organization, city, state) Harvard University, Cambridge, MA KEY PERSONNEL ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI053330-03
Application #
6830760
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Macchiarini, Francesca
Project Start
2003-06-15
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
3
Fiscal Year
2005
Total Cost
$369,000
Indirect Cost
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
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
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
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

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