%0 Journal Article
%T Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-¦Ã gene hypermethylation
%A Hui Li
%A Jie Ding
%A Lei Wang
%A Yixin Xia
%A Yushi Yao
%J -
%D 2017
%R 10.1371/journal.ppat.1006736
%X Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM), which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-¦Ã responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-¦Ã production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-¦Ã gene promoter region and decreased IFN-¦Ã production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-¦Ã gene hypermethylation and significantly reduced IFN-¦Ã production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-¦Ã-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-¦Ã gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy
%K Cytotoxic T cells
%K Progesterone
%K DNA methylation
%K Pregnancy
%K Mouse models
%K Spleen
%K T cells
%K Cell staining
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006736