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Reduced CCR4, interleukin-13 and GATA-3 up-regulation in response to type 2 cytokines of cord blood T lymphocytes in infants at genetic risk of type 1 diabetes
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Department of Clinical Microbiology, University of Kuopio, Kuopio and Immunogenetics Laboratory, University of Turku, Turku, Finland.
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
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2007 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 121, no 2, 189-196 p.Article in journal (Refereed) Published
Abstract [en]

Aberrancies in T-cell polarization including expression of chemokine receptors have been reported in human leucocyte antigen (HLA) class II associated autoimmune diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis. We asked whether these aberrancies are present at birth in newborn infants carrying the HLA risk haplotypes for T1D. Sixty-seven cord blood (CB) samples from infants were screened for T1D-associated HLA risk genotypes (HLA-DR4-DQ8 and/or DR3-DQ2 without protective alleles). CB lymphocytes were stimulated with phytohaemagglutinin in type 1 (interleukin (IL)-12, anti-IL4) or type 2 (IL-4, anti-IL12) cytokine environment for 6 days. The expression of chemokine and cytokine receptors on T cells was determined by flow cytometry, secretion of cytokines was analysed with enzyme-linked immunosorbent assay, and transcription factors were analysed using real-time reverse transcriptase–polymerase chain reaction. After culture of CB lymphocytes in type 2 cytokine environment newborn infants carrying DR4-DQ8 haplotype (n = 18) showed reduced percentage of CD4 T cells expressing CCR4 (P = 0·009) and the level of CCR4 mRNA was decreased (P = 0·008). In addition, lower secretion of IL-13 and expression of GATA-3 in CB lymphocytes cultured in type 2 cytokine environment were found in the infants with DR4-DQ8 haplotype (P = 0·020 and P = 0·004, respectively) in comparison to newborn infants without DR4-DQ8 and DR3-DQ2 haplotypes (n = 37). Poor in vitro induction of type 2 immune responses in newborn infants with DR4-DQ8 haplotype suggests that the HLA genotype associated with risk of autoimmunity may affect the T cell polarization already at birth, which in turn may contribute to the risk for autoimmunity later in life.

Place, publisher, year, edition, pages
2007. Vol. 121, no 2, 189-196 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-39758DOI: 10.1111/j.1365-2567.2007.02557.xLocal ID: 51126OAI: diva2:260607
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2012-10-02Bibliographically approved

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Skarsvik, SusanneVaarala, Outi
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