Expansion of functional natural killer cells in multiple tissue compartments of mice treated with flt3-ligand: Implications for anti-cancer and anti-viral therapy

Shaw, Samuel G., Maung, Adrian A., Steptoe, Raymond J., Thomson, Angus W. and Vujanovic, Nikola L. (1998) Expansion of functional natural killer cells in multiple tissue compartments of mice treated with flt3-ligand: Implications for anti-cancer and anti-viral therapy. Journal of Immunology, 161 6: 2817-2824.

Author Shaw, Samuel G.
Maung, Adrian A.
Steptoe, Raymond J.
Thomson, Angus W.
Vujanovic, Nikola L.
Title Expansion of functional natural killer cells in multiple tissue compartments of mice treated with flt3-ligand: Implications for anti-cancer and anti-viral therapy
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 1998-09-15
Sub-type Article (original research)
Volume 161
Issue 6
Start page 2817
End page 2824
Total pages 8
Place of publication Bethesda, MD
Publisher American Association of Immunologists
Language eng
Subject 110704 Cellular Immunology
Abstract The generation and activity of NK cells appear to be regulated by a particular set of cytokines. We examined the in vivo effects of recombinant human Flt3 ligand (Flt3-L), a recently cloned potent hemopoietic cytokine, on NK cell development in mice. Daily i.p. administration of Flt3-L consistently induced striking increases in both the absolute number and the total cytotoxic activity of mature nonactivated NK cells within various tissues. Dose- and time-dependent increases were observed in the bone marrow (~2- and ~11-fold, respectively), thymus (~2.8- and ~2.0-fold), blood (~11- and ~15-fold), spleen (~10- and ~9-fold), and liver (~15- and ~39-fold). In addition, IL-2 induced a rapid increase in NK activity, NK cell proliferative responses, generation of lymphokine-activated killer activity, and development of activated adherent NK cells, which were all significantly increased by Flt3-L treatment. Thus, in addition to its recently reported capacity to stimulate dendritic cell production, Flt3-L has a prominent biologic role in NK cell generation in vivo. This is probably a result of selectively induced expansion of NK cell progenitors (pro-NK cells), because Flt3-L stimulates in vitro proliferation of pro-NK cells without affecting the cytotoxicity of mature NK cells. The results also indicate that either alone or in combination with a potent activator of NK cells, such as IL-2, Flt3-L could be used to markedly augment the number and activity of NK cells, especially in the liver. Flt3-L appears to have considerable potential for therapy of both cancer and viral infection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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