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
2007 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 121, no 2, 189-196 p.Article in journal (Refereed) Published
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-39758DOI: 10.1111/j.1365-2567.2007.02557.xLocal ID: 51126OAI: oai:DiVA.org:liu-39758DiVA: diva2:260607