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Nutritional Immunology

Stimulation of the Immune Response in B6C3F1 Mice by Genistein Is Affected by Exposure Duration, Gender, and Litter Order¹

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 and ^* Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

²To whom correspondence should be addressed. E-mail: tlguo{at}hsc.vcu.edu.

The objective of this study was to determine whether immune responses could be differentially modulated by the phytoestrogen genistein (GEN) in mice from the 1st and 2nd litters, and whether the effects were persistent or reversible. B6C3F1 mice were exposed to a control or GEN-containing diet at 25, 250, and 1250 µg/g for the 1st litters, and 500 µg/g for the 2nd litters from d 0 of gestation to postnatal day (PND) 22, and through feeding after weaning. At PND42, anti-CD3 antibody-stimulated splenic T-cell proliferation and the percentages of T cells were increased in mice from the 1st litters at 250 and 1250 µg/g GEN but not from the 2nd litters. At PND84, the activity of IL-2-treated NK cells was significantly increased by GEN in mice from the 2nd litters but not from the 1st litters. The activity of cytotoxic T cells (CTLs) was also significantly increased by GEN in male mice from the 2nd litters. However, the increases in the CTL activity were not significant when the male mice were shifted from GEN-containing food to control food at PND22. Additionally, the increases in T-cell activities in female mice from the 1st litters and male mice from the 2nd litters were associated with a decrease in the percentage of CD4⁺CD25⁺ T regulatory cells. Overall, the results demonstrated that GEN could enhance the immune responses in mice from the 1st and 2nd litters; however, the effects varied depending on the exposure duration, gender, and litter order.

KEY WORDS: • genistein • developmental exposure • immune stimulation and litter order