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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, 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.

Editor: J. D. Clements

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

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