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CD4 + CD25 + regulatory T cells in human pregnancy: development of a T reg ‐MLC‐ELISPOT suppression assay and indications of paternal specific T regs
Author(s) -
Mjösberg Jenny,
Berg Göran,
Ernerudh Jan,
Ekerfelt Christina
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02529.x
Subject(s) - elispot , il 2 receptor , peripheral blood mononuclear cell , immunology , immune system , pregnancy , biology , cytokine , reproductive immunology , antibody , microbiology and biotechnology , andrology , t cell , medicine , in vitro , reproductive technology , genetics , lactation
Summary 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 (T reg ) 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 T reg cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL‐4 compared to controls. In pregnant and non‐pregnant controls, T reg cells suppressed IFN‐γ reactivity against paternal and unrelated alloantigens. Interestingly, T reg cells suppressed IL‐4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying T reg cells in antifetal cytokine reactions during pregnancy. Results indicate that T reg 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 T reg cells, which would allow for IL‐4, alongside CD4 + CD25 + T reg cells, to control potentially detrimental IFN‐γ reactions during pregnancy.