Tohoku J. Exp. Med., 2016 November, 240(3)

Early Pregnancy Factor Enhances the Generation and Function of CD4⁺CD25⁺ Regulatory T Cells

QUANGANG CHEN,¹ XIAORONG ZHU,¹ RENJIN CHEN,¹ JING LIU,² PENG LIU,³ ANKANG HU,¹ LIANLIAN WU,¹ HUI HUA⁴ and HONGHUA YUAN³

¹Laboratory Animal Center, Xuzhou Medical University, Xuzhou, Jiangsu, China
²Department of Respiratory Medicine, Xuzhou Central Hospital, Affiliated Xuzhou Hospital of Medical University of Southeast University, Xuzhou, Jiangsu, China
³Research Center for Neurobiology of Xuzhou Medical University, Xuzhou, Jiangsu, China
⁴Department of Pathogenic Biology and Immunology, Infection and Immunity Laboratory, Xuzhou Medical University, Xuzhou, Jiangsu, China

The mechanisms of fetal semi-allograft acceptance by the mother's immune system have been the target of many immunological studies. Early pregnancy factor (EPF) is a molecule present in the serum of pregnant mammals soon after conception that has been reported to have immunomodulatory effects. In the present study, we aimed to determine whether immune cells such as CD4⁺CD25⁺ regulatory T cells (Tregs) are involved in the suppressive mechanism of EPF. Accordingly, CD4⁺CD25⁻ T cells were isolated from spleens of female C57BL/6 mice and stimulated with anti-CD3 antibody, anti-CD28 antibody and IL-2 in the presence or absence of EPF. Flow cytometry was used to analyze the differentiation of CD4⁺CD25⁻ T cells to CD4⁺CD25⁺ Tregs. We thus found a remarkable rise in the Treg ratio in the EPF-treated cells. Higher mRNA and protein levels of fork head box P3 (Foxp3), a marker of the Treg lineage, were also observed in cells treated with EPF. Furthermore, the effect of EPF on Treg immunosuppressive capacity was evaluated. EPF treatment induced the expression of interleukin-10 and transforming growth factor β1 in Tregs. The suppressive capacity of Tregs was further measured by their capability to inhibit T cell receptor-mediated proliferation of CD4⁺CD25⁻ T cells. We thus found that EPF exposure can enhance the immunosuppressive functions of Tregs. Overall, our data suggest that EPF induces the differentiation of Tregs and increases their immunosuppressive activities, which might be an important mechanism to inhibit immune responses during pregnancy.

keywords —— cell function; early pregnancy factor; immune tolerance; immunomodulation; Treg cell

© 2016 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2016, 240, 215-220

Correspondence: Honghua Yuan, Research Center for Neurobiology of Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.

e-mail: jianling213@126.com