Abstract

NK cells defend against viral infections and cancer, but little is known about the bone marrow cells (BMC) that become NK cells. The over-all goal of this revised competitive renewal is to better define cells in early stages of NK cell development and the factors that control their function.
Aim 1 will focus on further characterization of the NK cell precursor by a] producing new mAbs selective for NK cell precursors; b] using the new and known mAbs to further enrich and define NK cell precursors in earlier and later stages of development.
Aim 2 will focus on the stromal interactions and factors which regulate function of NK cell precursors by a] evaluating the ability of specific stromal cell lines to support NK cell development and b] identifying stromal-precursor cell interactions and cytokines that regulate proliferation and/or differentiation of NK cell precursors. These studies will provide needed information to evaluate the effects of various clinical treatments or conditions on NK cell precursors, and to manipulate the proliferation and differentiation of these precursors for therapeutic gain.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA055705-05A1
Application #
2007990
Study Section
Experimental Immunology Study Section (EI)
Project Start
1992-07-09
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Jensen, Majken K; Koh-Banerjee, Pauline; Hu, Frank B et al. (2004) Intakes of whole grains, bran, and germ and the risk of coronary heart disease in men. Am J Clin Nutr 80:1492-9
Lu, J; Patrene, K D; Herberman, R B et al. (1999) Expression of murine CD34 by fetal liver NK cell progenitors. Exp Hematol 27:272-81
Lu, J; Patrene, K D; Appasamy, P M et al. (1999) Characterization of the stage in natural killer cell development in 14.5-day mouse fetal liver using adult bone marrow stroma. Exp Hematol 27:1046-56
Yaroslavskiy, B; Colson, Y; Ildstad, S et al. (1998) Addition of a bone marrow ""facilitating cell"" population increases stem cell-derived cobblestone area formation in impaired long-term bone marrow culture stroma. Exp Hematol 26:604-11
Boggs, S S; Trevisan, M; Patrene, K et al. (1998) Lack of natural killer cell precursors in fetal liver of Ikaros knockout mutant mice. Nat Immun 16:137-45
Delfino, D V; Patrene, K D; Lu, J et al. (1996) Natural killer cell precursors in the CD44neg/dim T-cell receptor population of mouse bone marrow. Blood 87:2394-400
Kawachi, I; Colditz, G A; Ascherio, A et al. (1996) A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA. J Epidemiol Community Health 50:245-51
Boggs, S S; Patrene, K D; Mueller, G M et al. (1995) Prolonged systemic expression of human IL-1 receptor antagonist (hIL-1ra) in mice reconstituted with hematopoietic cells transduced with a retrovirus carrying the hIL-1ra cDNA. Gene Ther 2:632-8
Delfino, D V; Patrene, K D; DeLeo, A B et al. (1994) Role of CD44 in the development of natural killer cells from precursors in long-term cultures of mouse bone marrow. J Immunol 152:5171-9
Kawachi, I; Colditz, G A; Ascherio, A et al. (1994) Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 89:1992-7

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