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Phenotypic and functional studies of NK cells in neonates and during early childhood
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
Responsible organisation
2008 (English)Doctoral thesis, monograph (Other academic)
Abstract [en]

During infancy, before adaptive immunity has matured, innate immunity is thought to be relatively more important. Human natural killer (NK) cells are innate immune cells involved in the control of virus-infected cells and can influence adaptive immunity mainly through cytokine production. This thesis aimed at investigating function and phenotype of NK cells in children from birth and during early childhood and to see if these features are altered in children that develop early allergy, in children latently infected by herpes viruses or born by preeclamptic mothers.

Our results suggest that NK-cell populations are dynamic during the first years of life and start to resemble the phenotype of adults after five years of age. Early alterations in the NK-cell populations could lead to insufficient Th1 priming, with an increased risk to develop allergic disease. Early infection by common herpes viruses can influence NK-cell function and might be one important factor involved in early maturation processes of adaptive immunity. The altered NK-cell function and cytokine levels, noticed in CB from pathological pregnancies, suggest that NK cells could be influenced already in utero. These early alterations of innate immunity may affect the development of the child’s immune system, sometimes with beneficial outcome but could in some cases promote pathology.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2008. , 90 p.
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-8258ISBN: 978-91-7155-747-6 (print)OAI: oai:DiVA.org:su-8258DiVA: diva2:199920
Public defence
2008-11-07, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-10-16 Created: 2008-10-16Bibliographically approved
List of papers
1. The expression of human natural killer cell receptors in early life
Open this publication in new window or tab >>The expression of human natural killer cell receptors in early life
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2007 In: Scandinavian Journal of Immunology, ISSN 0300-9475, Vol. 66, no 2/3, 335-344 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25534 (URN)
Note
Part of urn:nbn:se:su:diva-8258Available from: 2008-10-16 Created: 2008-10-16Bibliographically approved
2. A decreased proportion of CD56bright human natural killer cells in cord blood from children that develop early allergy
Open this publication in new window or tab >>A decreased proportion of CD56bright human natural killer cells in cord blood from children that develop early allergy
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25535 (URN)
Note
Part of urn:nbn:se:su:diva-8258Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2010-01-13Bibliographically approved
3. Herpesvirus seropositivity in childhood associates with decreased monocyte-induced NK-cell IFN-γ production
Open this publication in new window or tab >>Herpesvirus seropositivity in childhood associates with decreased monocyte-induced NK-cell IFN-γ production
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2009 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 182, no 4, 2511-2517 p.Article in journal (Refereed) Published
Abstract [en]

EBV infection is inversely associated with IgE sensitization in children, and this association is further enhanced by CMV coinfection. In mice, herpesvirus latency causes systemic innate activation and protection from bacterial coinfection, implying the importance of herpesviruses in skewing immune responses during latent infection. Early control of viral infections depends on IFN- release by NK cells, which generally requires the presence of accessory cells. We investigated IFN- production by NK cells in PBMCs from children seropositive (SP) for EBV alone, for both EBV and CMV, or seronegative for both viruses. The ability of classical (CD14++CD16–) and proinflammatory (CD14+CD16+) monocytes to induce autologous NK cell IFN- was studied by coculture experiments with enriched CD3–CD56+ cells. Transwell experiments were used to evaluate how monocytes interact with NK cells to induce IFN- synthesis. SP children had a significantly reduced proportion of IFN-+ NK cells and cognate intracellular IFN- levels, which was more pronounced in CMV-coinfected subjects. Also, resting PBMCs of SP children displayed lower proportions of proinflammatory monocytes. IFN- production by NK cells was dependent on interactions with monocytes, with the proinflammatory subset inducing the highest IFN-. Finally, SP children had markedly lower levels of plasma IFN-, concurrent with in vitro findings. Herpesvirus infections could be one contributing factor for maturation toward balanced Th1-Th2 responses. Our data indicate that early infection by herpesviruses may affect NK cell and monocyte interactions and thereby also influence the development of allergies.

National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-25536 (URN)10.4049/jimmunol.0801699 (DOI)000263126300082 ()19201907 (PubMedID)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-13Bibliographically approved

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