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Harner, S. ; Nößner, E. ; Nadas, K.* ; Leumann-Runge, A.* ; Schiemann, M. ; Faber, F.L.* ; Heinrich, J. ; Krauss-Etschmann, S.

Cord blood Vα24-vβ11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses.

PLoS ONE 9:e15714 (2011)
Verlagsversion Volltext DOI PMC
Open Access Gold
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BACKGROUND: The fetal immune system is characterized by a Th2 bias but it is unclear how the Th2 predominance is established. Natural killer T (NKT) cells are a rare subset of T cells with immune regulatory functions and are already activated in utero. To test the hypothesis that NKT cells are part of the regulatory network that sets the fetal Th2 predominance, percentages of Vα24(+)Vβ11(+) NKT cells expressing Th1/Th2-related chemokine receptors (CKR) were assessed in cord blood. Furthermore, IL-4 and IFN-γ secreting NKT cells were quantified within the single CKR(+) subsets.RESULTS: Cord blood NKT cells expressed the Th2-related CCR4 and CCR8 at significantly higher frequencies compared to peripheral blood NKT cells from adults, while CXCR3(+) and CCR5(+) cord blood NKT cells (Th1-related) were present at lower percentages. Within CD4(neg)CD8(neg) (DN) NKT cells, the frequency of IL-4 producing NKT cells was significantly higher in cord blood, while frequencies of IFN-γ secreting DN NKT cells tended to be lower. A further subanalysis showed that the higher percentage of IL-4 secreting DN NKT cells was restricted to CCR3(+), CCR4(+), CCR5(+), CCR6(+), CCR7(+), CCR8(+) and CXCR4(+) DN subsets in cord blood. This resulted in significantly decreased IFN-γ /IL-4 ratios of CCR3(+), CCR6(+) and CCR8(+) cord blood DN NKT cells. Sequencing of VA24AJ18 T cell receptor (TCR) transcripts in sorted cord blood Vα24Vβ11 cells confirmed the invariant TCR alpha-chain ruling out the possibility that these cells represent an unusual subset of conventional T cells. CONCLUSIONS: Despite the heterogeneity of cord blood NKT cells, we observed a clear Th2-bias at the phenotypic and functional level which was mainly found in the DN subset. Therefore, we speculate that NKT cells are important for the initiation and control of the fetal Th2 environment which is needed to maintain tolerance towards self-antigens as well as non-inherited maternal antigens.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Invariant NKT cells; Cutting edge; Dendritic cells; Alpha-chain; Lymphocytes; Subsets; CD4(+); Requirements; Environment; Individuals
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: e15714 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
Institute of Molecular Immunology (IMI)
Institute of Virology (VIRO)
Institute of Epidemiology (EPI)
CCG Immune Monitoring (Platform) (IMI-KIM)
POF Topic(s) 30202 - Environmental Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Lung Research
Immune Response and Infection
Genetics and Epidemiology
PSP-Element(e) G-501600-003
G-501700-001
G-520100-001
G-503900-001
G-501790-003
G-520400-001
G-501790-002
G-501790-001
PubMed ID 21305060
DOI 10.1371/journal.pone.0015714
WOS ID WOS:000286834300023
Scopus ID 79551680268
Erfassungsdatum 2011-06-22
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