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Infection and Immunity, February 2006, p. 1106-1112, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1106-1112.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Dendritic Cell Immaturity during Infancy Restricts the Capacity To Express Vaccine-Specific T-Cell Memory

John W. Upham,* Angela Rate, Julie Rowe, Merci Kusel, Peter D. Sly, and Patrick G. Holt

Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia

Received 1 September 2005/ Returned for modification 29 September 2005/ Accepted 11 November 2005

The capacity of the immune system in infants to develop stable T-cell memory in response to vaccination is attenuated, and the mechanism(s) underlying this developmental deficiency in humans is poorly understood. The present study focuses on the capacity for expression of in vitro recall responses to tetanus and diphtheria antigens in lymphocytes from 12-month-old infants vaccinated during the first 6 months of life. We demonstrate that supplementation of infant lymphocytes with "matured" dendritic cells (DC) cultured from autologous CD14+ precursors unmasks previously covert cellular immunity in the form of Th2-skewed cytokine production. Supplementation of adult lymphocytes with comparable prematured autologous DC also boosted vaccine-specific T-cell memory expression, but in contrast to the case for the infants, these cytokine responses were heavily Th1 skewed. Compared to adults, infants had significantly fewer circulating myeloid DC (P < 0.0001) and plasmacytoid DC (P < 0.0001) as a proportion of peripheral blood mononuclear cells. These findings suggest that deficiencies in the numbers of antigen-presenting cells and their functional competence at 12 months of age limit the capacity to express effector memory responses and are potentially a key factor in reduced vaccine responsiveness in infants.

* Corresponding author. Mailing address: Telethon Institute for Child Health Research, P.O. Box 855, West Perth, Western Australia 6872, Australia. Phone: 61 8 9489 7777. Fax: 61 8 9489 7700. E-mail: johnu{at}ichr.uwa.edu.au.

Editor: J. T. Barbieri

Infection and Immunity, February 2006, p. 1106-1112, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1106-1112.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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