The Journal of Experimental Medicine
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Published 18 November 2002. doi:10.1084/jem.20020943
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© Rockefeller University Press, 0022-1007/2002/11/1381/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 10, November 18, 2002 1381-1386

Brief Definitive Report

 Age at First Viral Infection Determines the Pattern of T Cell–mediated Disease during Reinfection in Adulthood

Fiona J. Culley, Joanne Pollott and Peter J.M. Openshaw

Department of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology, and Medicine, London W2 1PG, United Kingdom

Address correspondence to P.J.M. Openshaw, Dept. of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology, and Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, UK. Phone: 44-020-7594-3854; Fax: 44-020-7262-8913; E-mail: p.openshaw{at}ic.ac.uk

Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased frequency of wheeze and asthma in later childhood. Since most severe RSV infections occur between the 8th and 24th postnatal week, we examined whether age at first infection determines the balance of cytokine production and lung pathology during subsequent rechallenge. Primary RSV infection in newborn mice followed the same viral kinetics as in adults but was associated with reduced and delayed IFN-{gamma} responses. To study rechallenge, mice were infected at 1 day or 1, 4, or 8 weeks of age and reinfected at 12 weeks. Neonatal priming produced more severe weight loss and increased inflammatory cell recruitment (including T helper 2 cells and eosinophils) during reinfection, whereas delayed priming led to enhanced interferon {gamma} production and less severe disease during reinfection. These results show the crucial importance of age at first infection in determining the outcome of reinfection and suggest that the environment of the neonatal lung is a major determinant of cytokine production and disease patterns in later life. Thus, simply delaying RSV infection beyond infancy might reduce subsequent respiratory morbidity in later childhood.

Key Words: bronchiolitis • asthma • immunity • pneumovirinae • virus


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