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Infection and Immunity, December 2002, p. 6583-6588, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6583-6588.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Development of Interleukin-12-Producing Capacity throughout Childhood

John W. Upham,1,2* Peter T. Lee,1,{dagger} Barbara J. Holt,1 Tricia Heaton,1 Susan L. Prescott,1,3 Mary J. Sharp,1 Peter D. Sly,1 and Patrick G. Holt1

Telethon Institute for Child Health Research and Centre for Child Health Research,1 Departments of Medicine,2 Paediatrics, University of Western Australia, Perth, Australia3

Received 13 May 2002/ Returned for modification 10 July 2002/ Accepted 3 September 2002

Increasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy individuals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killed Staphylococcus aureus was markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR+ cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells.

* Corresponding author. Mailing address: Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth WA 6872, Australia. Phone: 618-9489-7839. Fax: 618-9489-7700. E-mail: johnu{at}ichr.uwa.edu.au.

Editor: J. D. Clements

{dagger} Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

Infection and Immunity, December 2002, p. 6583-6588, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6583-6588.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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