Maternal Lipopolysaccharide Exposure Promotes Immunological Functional Changes in Adult Offspring CD4+ T Cells

Am J Reprod Immunol. 2015 Jun;73(6):522-35. doi: 10.1111/aji.12364. Epub 2015 Jan 30.


Problem: Maternal immune activation (MIA) is a risk factor for autism and schizophrenia. However, how MIA affects offspring immune function remains unknown.

Method of study: To investigate the effect of MIA on the offspring, pregnant C57BL/6J mice were given an intraperitoneal injection of 50 μg/kg lipopolysaccharide (LPS) on gestational day 12.5.

Results: Adult LPS-treated offspring were hyper-reactive to LPS, and enhanced tumor necrosis factor-α production was observed. CD4+ T cells from LPS offspring had an elevated percentage of interferon (IFN)-γ(+) CD4+ T cells and interleukin (IL)-17A+ CD4+ T cells in the spleen, IL-17A+ CD4+ T cells in the liver, and CD4+ Foxp3+ T cells in the spleen. LPS offspring CD4+ T cells showed increased proliferation and an enhanced survival rate. DNA microarray analysis of resting LPS offspring CD4+ T cells identified eight up-regulated genes, most of which encoded transcription factors. Quantitative liquid chromatography-mass spectrometry identified 18 up-regulated proteins in resting LPS offspring CD4+ T cells and five up-regulated proteins in activated LPS offspring CD4+ T cells, most of which participated in the PANTHER Gene Ontology metabolic process.

Conclusions: Our results showed that MIA to LPS up-regulated proteins involved in metabolic process in CD4+ T cells from LPS offspring that might contribute to the hyperactivated immune response of adult LPS offspring.

Keywords: CD4+ T cells study; lipopolysaccharide; maternal immune activation; mouse model; offspring immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / immunology
  • Autistic Disorder / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Lipopolysaccharides / toxicity*
  • Maternal Exposure / adverse effects*
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / immunology*
  • Prenatal Exposure Delayed Effects / pathology


  • Il17a protein, mouse
  • Interleukin-17
  • Lipopolysaccharides
  • Interferon-gamma