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In vivo immunomodulation following intradermal injection with DNA encoding IL-18

Lookup NU author(s): Dr Laurent Kremer

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Abstract

IL-18, a recently identified cytokine synthesized by different cell types, including Kupffer cells, activated macrophages, and keratinocytes, induces IFN-γ production by T cells and NK cells. The cDNA encoding IL-18 with its natural signal peptide was cloned under control of the CMV promoter and injected into the skin of mice. A single intradermal injection of this construction led to efficient in vivo expression of IL-18 in cutaneous dermal cells and induced IFN-γ mRNA production, indicating that it was produced in a biologically active form. In addition, a massive cellular infiltrate was observed in the skin 2 days after injection. When the mice were subsequently infected with Mycobacterium boris bacillus Calmette-Guerin (BCG), they produced lower levels of anti-BCG Abs than control animals. However, in contrast to their lowered humoral immune response, the mice produced higher amounts of Ag-specific IFN-γ after in vitro restimulation, as compared with the controls. Therefore, injection of DNA encoding IL-18 into the skin modulates both Ag-specific humoral and T cell responses upon mycobacterial infection. It increases the Th1 type response, which may be particularly useful for the development of new immunotherapeutic or immunoprotective approaches against infections by intracellular parasites, such as mycobacteria.


Publication metadata

Author(s): Kremer L, Dupre L, Wolowczuk I, Locht C

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 1999

Volume: 163

Issue: 6

Pages: 3226-3231

Print publication date: 15/09/1999

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://www.jimmunol.org/content/163/6/3226

PubMed id: 10477591


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