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Clinical and Diagnostic Laboratory Immunology, September 2004, p. 879-888, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.879-888.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interleukin-15 Enhances Cytotoxicity, Receptor Expression, and Expansion of Neonatal Natural Killer Cells in Long-Term Culture

Sunwoong S. Choi, Vaninder S. Chhabra, Quoc H. Nguyen, Bonnie J. Ank, E. Richard Stiehm, and Robert L. Roberts*

Department of Pediatrics, UCLA Medical Center, Los Angeles, California

Received 9 October 2003/ Returned for modification 15 December 2003/ Accepted 8 June 2004

Newborn infants have a higher susceptibility to various pathogens due to developmental defects in their host defense system, including deficient natural killer (NK) cell function. In this study, the effects of interleukin-15 (IL-15) on neonatal NK cells was examined for up to 12 weeks in culture. The cytotoxicity of fresh neonatal mononuclear cells (MNC) as assayed by K562 cell killing is initially much less than that of adult MNC but increases more than eightfold after 2 weeks of culture with IL-15 to a level equivalent to that of adult cells. This high level of cytotoxicity was maintained for up to 12 weeks. In antibody-dependent cellular cytotoxicity (ADCC) assays using CEM cells coated with human immunodeficiency virus gp120 antigen, IL-15 greatly increased ADCC lysis by MNC from cord blood. IL-15 increased expression of the CD16+ CD56+ NK markers of cord MNC fivefold after 5 weeks of incubation. Cultures of neonatal MNC with IL-15 for up to 10 weeks resulted in a unique population of CD3– CD8+ CD56+ cells (more than 60%), which are not present in fresh cord MNC. These results show that IL-15 can stimulate neonatal NK cells and sustain their function for several weeks, which has implications for the clinical use of IL-15.

* Corresponding author. Mailing address: Department of Pediatrics, UCLA Medical Center, MDCC 22-387, 10833 Le Conte Ave., Los Angeles, CA 90095. Phone: (310) 825-6777. Fax: (310) 825-9832. E-mail: rroberts{at}mednet.ucla.edu.

Clinical and Diagnostic Laboratory Immunology, September 2004, p. 879-888, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.879-888.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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