title: Early Pregnancy Factor Enhances the Generation and Function of CD4+CD25+Regulatory T Cells.
abstract: 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.
authors.affiliation: Laboratory Animal Center, Xuzhou Medical University.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Chen
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhu
authors.forename: Renjin
authors.initials: R
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Ankang
authors.initials: A
authors.lastname: Hu
authors.forename: Lianlian
authors.initials: L
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.forename: Honghua
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D018835:Chaperonin 10 / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D018835:Chaperonin 10; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D011257:Pregnancy Proteins; D011948:Receptors, Antigen, T-Cell; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor