CD4+ CD25+ regulatory T cells in human pregnancy: development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs
Article first published online: 11 JAN 2007
Volume 120, Issue 4, pages 456–466, April 2007
How to Cite
Mjösberg, J., Berg, G., Ernerudh, J. and Ekerfelt, C. (2007), CD4+ CD25+ regulatory T cells in human pregnancy: development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs. Immunology, 120: 456–466. doi: 10.1111/j.1365-2567.2006.02529.x
- Issue published online: 11 JAN 2007
- Article first published online: 11 JAN 2007
- Received 10 August 2006; revised 1 November 2006; accepted 2 November 2006.
- reproductive immunology;
- regulatory T cells (Treg);
- T cells, T helper type 1 and type 2 cells
The current study was aimed at developing a one-way mixed leucocyte culture–enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4+ CD25+ regulatory T (Treg) cells and applying this method in the study of antifetal immune reactions during human pregnancy. Twenty-one pregnant women and the corresponding fathers-to-be, and 10 non-pregnant control women and men, participated in the study. CD4+ CD25+ cells were isolated from peripheral blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin-4 (IL-4) and interferon-γ (IFN-γ) from responder cells, with or without the presence of autologous Treg cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL-4 compared to controls. In pregnant and non-pregnant controls, Treg cells suppressed IFN-γ reactivity against paternal and unrelated alloantigens. Interestingly, Treg cells suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying Treg cells in antifetal cytokine reactions during pregnancy. Results indicate that Treg cells contribute to strict regulation of both T helper type 1-like and type 2-like antifetal immune reactions. Interestingly, T helper type 2-like cells specific to unrelated alloantigens are able to escape the suppression of Treg cells, which would allow for IL-4, alongside CD4+ CD25+ Treg cells, to control potentially detrimental IFN-γ reactions during pregnancy.