Abstract
AbstractWe investigated whether a developmental immaturity of the dendritic cells (DCs) compartment could contribute to the high susceptibility to infections observed in newborns. DCs are among the first cells to colonize the spleen, but the ontogeny of DC subsets follows distinct steps. At birth, plasmacytoid DCs and CD4-CD8α- DCs are found in the spleen, whereas CD8α+ and CD4+ DCs are not present. Then, the CD8α+ DC compartment quickly develops and reaches an adult size by day 7, whereas the CD4+ DC compartment slowly increases to become predominant by the age of 3 weeks. The production of interleukin (IL)–12p70 by DCs is particularly efficient after birth, reflecting the stronger capacity of the neonatal CD8α- DCs to secrete IL-12 compared with its adult counterpart. Like-wise, neonatal DCs produced type I and II interferons. In vivo, following microbial stimulation, up-regulation of major histocompatibility complexes (MHCs) and of costimulatory molecules on DCs was induced clearly showing the activation of neonatal DCs in the neonatal environment. Therefore, despite a markedly different DC subset composition in early life compared with the adult DC compartment, neonatal DCs are fully competent in their innate immune functions.
Highlights
We investigated whether a developmental immaturity of the dendritic cells (DCs) compartment could contribute to the high susceptibility to infections observed in newborns
Despite a markedly different DC subset composition in early life compared with the adult DC compartment, neonatal DCs are fully competent in their innate immune functions. (Blood. 2003;102:585-591)
In order to document how and when DCs arise in the spleen, we performed an immunohistochemical staining of DCs together with B or T cells during the first week of life
Summary
We investigated whether a developmental immaturity of the dendritic cells (DCs) compartment could contribute to the high susceptibility to infections observed in newborns. A recent report indicates that the spleen of murine newborns might contain only a few number of DCs, with a majority of CD11cϪ DC–like population lacking MHC II expression.[10] more recently, we showed that, at 7 days of life, a substantial number of CD11cϩ DCs are present in the spleen and that these cells are able to induce cytotoxic T lymphocyte (CTL) responses in adult recipient mice.[11] Here, in order to better understand neonatal immune responses, we analyzed in detail the ontogeny of CD11cϩ DCs and their capacity to provide innate responses to microbial stimuli in early life. The present report gives important insights into the development of the DC compartment and shows that neonatal DCs can efficiently respond to microbial agents
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