Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2006 Dec;146(3):493-502.
doi: 10.1111/j.1365-2249.2006.03243.x.

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

Affiliations
Multicenter Study

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

B C Holm et al. Clin Exp Immunol. 2006 Dec.

Abstract

Maternal transmission of islet autoantibodies to children born to mothers with type 1 diabetes (T1D) has been shown to protect from autoantibodies and diabetes development later in life. However, the factors conferring disease protection are poorly understood. The aim of this study was to evaluate comparatively proinflammatory cytokines, autoantibodies and lymphocyte subsets in cord blood (CB) of children born to mothers with either T1D (n = 13), gestational diabetes (GDM) (n = 32) or healthy mothers (n = 81) in relation to transplacental passage of autoantibodies. The results are consistent with early priming of the fetal immune system only in children born to mothers with T1D. Levels of interleukin (IL)-1beta (P = 0.022), tumour necrosis factor (TNF)-alpha (P = 0.002) and IL-8 (P = 0.0012), as well as the frequency of CD4(+) CD25(+) T cells (P < 0.01) were significantly increased, and the increased levels correlated positively with anti-GAD65 autoantibody (GADA) levels. Moreover, CD4(+) CD25(+) T cells of children born to T1D mothers exhibited a more pronounced memory phenotype with increased CCR4 expression and down-regulation of CD62L. These data suggest that early activation of the fetal immune system as a consequence of maternal autoimmunity and transplacental passage of GADA may influence the generation and expansion of fetal regulatory T cells. This might induce an early antigen-specific immunological tolerance that could protect against T1D later in life.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flow cytometric analysis of cord blood lymphocytes. Cumulative analysis of the frequency of natural killer (NK) cells (defined by the expression of both CD16 and CD56 markers) (a), CD4+ CD25+ T cells (b), CD4+ CD25+ CCR4+ T cells (c) and CD4+ CD25+ CD62Llo CCR4hi (d) in cord blood of children born to healthy mothers (healthy, open squares), children born to mothers with gestational diabetes (GDM, open triangles) and with type 1 diabetes (T1D, open circles). Median values for each patient group are marked with a horizontal line. P-values < 0·0167 were considered significant after Bonferroni correction. *P < 0·05, **P < 0·0167, ***P < 0·001.
Fig. 2
Fig. 2
Expression of forkhead box P3 (FOXP3) in cord blood (CB) and adult CD4+ CD25+ T cells. Representative flow cytometry analysis of CD4+ CD25+ T cells from cord and adult peripheral blood of healthy donors. Cells were stained with peridinin chlorophyll (PerCP)-labelled CD4, fluorescein isothiocyanate (FITC)-labelled CD25 and antigen-presenting cell (APC)-labelled FOXP3 monoclonal antibodies. The oval region depicting CD4+ T cells expressing high levels of CD25 in the dot plot from adult blood is the same used for the cord blood dot plot.

Similar articles

Cited by

References

    1. Pociot F, McDermott MF. Genetics of type 1 diabetes mellitus. Genes Immun. 2002;3:235–49. - PubMed
    1. Itoh N, Hanafusa T, Miyazaki A, et al. Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest. 1993;92:2313–22. - PMC - PubMed
    1. Peakman M, Wen L, McNab GL, Watkins PJ, Tan KC, Vergani D. T cell clones generated from patients with type 1 diabetes using interleukin-2 proliferate to human islet antigens. Autoimmunity. 1994;17:31–9. - PubMed
    1. Dahlquist GG, Ivarsson S, Lindberg B, Forsgren M. Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study. Diabetes. 1995;44:408–13. - PubMed
    1. Dahlquist G, Blom L, Lonnberg G. The Swedish Childhood Diabetes Study – a multivariate analysis of risk determinants for diabetes in different age groups. Diabetologia. 1991;34:757–62. - PubMed

Publication types