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. See instructions. Use continuation pages as needed to provide the required information Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Strominger, Jack L. Harvard University Boyson, Jonathan Harvard University Koopman, Louise Harvard University in the format shown below. Role on Project Principal Investigator Postdoctoral Research Fellow Postdoctoral Research Fellow Disclosure Permission Statement. Applicable to CBIR/STTR Only. See instructions. [] Yes [] No PHS398(Rev. 05/01) Paae 2 Form Paoe 2 _ Principal Investigator/Program Director (Last, first, middle): Strominqer, Jack L. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page ......................................................................................................................................................... 1 Description,

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI053330-05
Application #
7149145
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Prabhudas, Mercy R
Project Start
2003-06-15
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2008-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$349,879
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
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; 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
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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