Abstract

Neonates are clearly more susceptible to severe disease following infection with a variety of pathogens than are adults. However, the causes for this are unclear and are often attributed to immunological immaturity. While several aspects of immunity differ between adults and neonates, the capacity of dendritic cells in neonates to process and present antigen to CD8+ T cells remains to be addressed. We used human CD8+ T cell clones to compare the ability of neonatal and adult monocyte-derived dendritic cells to present or process and present antigen using the MHC class I pathway. Specifically, we assessed the ability of dendritic cells to present antigenic peptide, present an HLA-E–restricted antigen, process and present an MHC class I-restricted antigen through the classical MHC class I pathway, and cross present cell-associated antigen via MHC class I. We found no defect in neonatal dendritic cells to perform any of these processing and presentation functions and conclude that the MHC class I antigen processing and presentation pathway is functional in neonatal dendritic cells and hence may not account for the diminished control of pathogens.

Highlights

  • About 2 million children die each year of infectious diseases (World Health Organization Maternal Health and Safe Motherhood Programme MSM96.7, 1996)

  • To address the hypothesis that the increased severity of disease associated with neonates is due to a defect in Dendritic cells (DC) MHC I antigen processing and presentation, we performed a comprehensive study using monocyte-derived DC isolated from neonatal cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC)

  • The most comprehensive study of MHC II antigen processing and presentation function in neonates was performed using cord blood-derived monocytes as APC

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Summary

Introduction

About 2 million children die each year of infectious diseases (World Health Organization Maternal Health and Safe Motherhood Programme MSM96.7, 1996). The causes for this are likely to be pleomorphic, and include the reduced frequency and diminished functional capacity of neonatal T cells [3] While studies in both humans and mice demonstrate decreased T cell function in neonates, this defect can be overcome by the administration of strong adjuvants [4]. We assessed the ability of DC to present antigenic peptide, present a MHC class Ib (HLA-E)restricted antigen, process and present a MHC class Ia antigen delivered through viral infection, and cross present cellassociated antigen This thorough functional examination of neonatal DC demonstrates that these cells are fully competent APC in their ability to process and present antigen to CD8+ T cells

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