title: Dendritic cell immaturity during infancy restricts the capacity to express vaccine-specific T-cell memory.
abstract: 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.
authors.affiliation: Telethon Institute for Child Health Research, P.O. Box 855, West Perth, Western Australia 6872, Australia. johnu@ichr.uwa.edu.au
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.forename: Angela
authors.initials: A
authors.lastname: Rate
authors.forename: Julie
authors.initials: J
authors.lastname: Rowe
authors.forename: Merci
authors.initials: M
authors.lastname: Kusel
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004168:Diphtheria Toxoid / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D016207:Cytokines; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D013745:Tetanus Toxoid