NK cells are hematopoietic cells with the ability to kill a variety of tumors and to secrete immunoregulatory molecules with diverse effects over other hematopoietic lineages. Physiologically, they have been implicated in the clearance of intracellular pathogens, in the surveillance and destruction of newly developed tumors, and are the main effectors responsible for the rejection of bone marrow grafts. In addition, they have the potential to be utilized as vectors carrying different biological functions in adoptive immunotherapy protocols. NK cells are derived form bone marrow progenitors, through a probable common lymphoid progenitor. Phenotypically, they express on their surface a variety of molecules present in other hematopoietic lineages, as cell as NK lineage restricted markers. In addition it seems to be a defined distribution in the expression of markers in NK cells isolated from different tissues. The implications of this heterogeneity has not been studied extensively, in part by the lack of information on committed progenitors, by the low numbers of NK cells compared with the other lymphoid cells, and by the inability to generate and maintain clonal populations of NK cells in culture. The understanding of the development, heterogeneity and function of this compartment is important if we would like to design protocols aimed to modulate or alter NK cell functions in order to obtain better protection against pathogens, diminished reactivities against allogeneic hematopoietic grafts, and better immunotherapeutic vectors. The present application proposes to study the heterogeneity of the murine NK cell compartment from a developmental as well as form a functional prospective. Three main aims are considered: 1. To isolate and characterize NK cell committed progenitors from adult bone marrow. 2. To define the phenotype and functional heterogeneity of the NK cell compartment. 3. To establish methods to grow and propagate clonal cell lines of murine NK cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI046708-02
Application #
6374395
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Nabavi, Nasrin N
Project Start
2000-07-01
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$208,950
Indirect Cost
Name
University of Connecticut
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Mathias, C B; Guernsey, L A; Zammit, D et al. (2014) Pro-inflammatory role of natural killer cells in the development of allergic airway disease. Clin Exp Allergy 44:589-601
Khosla, Sundeep (2007) Re: ""The 3.6 kb DNA fragment from the rat Col1a1 gene promoter drives the expression of genes in both osteoblast and osteoclast lineage cells"" by Boban et al. (Bone 39:1302-1312, 2006). Bone 40:1671-2;author reply 1673-4
Boban, Ivana; Jacquin, Claire; Prior, Katie et al. (2006) The 3.6 kb DNA fragment from the rat Col1a1 gene promoter drives the expression of genes in both osteoblast and osteoclast lineage cells. Bone 39:1302-12
Jacquin, Claire; Gran, Diane E; Lee, Sun Kyeong et al. (2006) Identification of multiple osteoclast precursor populations in murine bone marrow. J Bone Miner Res 21:67-77
Aguila, Hector Leonardo; Rowe, David W (2005) Skeletal development, bone remodeling, and hematopoiesis. Immunol Rev 208:7-18
Schluns, Kimberly S; Nowak, Elizabeth C; Cabrera-Hernandez, Arturo et al. (2004) Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor alpha expression. Proc Natl Acad Sci U S A 101:5616-21
Visnjic, Dora; Kalajzic, Zana; Rowe, David W et al. (2004) Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103:3258-64
Katavic, Vedran; Grcevic, Danka; Lee, Sun Kyeong et al. (2003) The surface antigen CD45R identifies a population of estrogen-regulated murine marrow cells that contain osteoclast precursors. Bone 32:581-90
Cooper, Megan A; Bush, Jennifer E; Fehniger, Todd A et al. (2002) In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100:3633-8