Phenotypic and Epigenetic Adaptations of Cord Blood CD4+ T Cells to Maternal Obesity

Area of Science:

• Immunology
• Developmental Biology
• Reproductive Health

Background:

• Pregravid obesity negatively affects offspring immune development and infection susceptibility.
• Mechanisms of maternal obesity's impact on fetal myeloid cells are emerging, but effects on T cells are unclear.

Purpose of the Study:

• To investigate the consequences of maternal obesity on fetal CD4 T cell phenotype and function.
• To explore potential epigenetic mechanisms linking maternal obesity to fetal immune reprogramming.

Main Methods:

• Collected umbilical cord blood from infants of lean and obese mothers.
• Utilized flow cytometry and single-cell RNA sequencing to profile CD4 T cells.
• Assessed T cell responses following ex vivo polyclonal stimulation.

Main Results:

• Maternal obesity correlated with increased frequencies of memory CD4 T cells, indicating in vivo activation.
• Single-cell RNA sequencing revealed an expanded, activated memory T cell subset in infants of obese mothers.
• Ex vivo stimulation showed impaired cytokine responses, suggesting functional defects in CD4 T cells.

Conclusions:

• Maternal obesity induces phenotypic and functional aberrations in fetal CD4 T cells.
• Epigenetic changes in lymphocyte activation and T cell receptor signaling loci may underlie these immune alterations.
• These findings provide a potential explanation for increased microbial infection susceptibility in infants born to obese mothers.