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

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.