Immunosuppression detected in pregnant mice by rosette inhibition test

Zhu

et al. 2016

Tohoku J. Exp. Med.

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.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhu

et al. 2016

Tohoku J. Exp. Med.

“…The earliest specific indication for fertilization and the continuing presence of a viable conceptus is a serum constituent, which has been originally detected in mice [38]. This substance is known as EPF (early pregnancy factor) and has also been described in women [39], sheep [40], cattle [41] and pigs [42].…”

Section: Early Pregnancy Factor (Epf)mentioning

confidence: 99%

Recent Possibilities for the Diagnosis and Pharmacological Control of Pregnancy Loss in Dairy Cow

Szenci¹

2015

JLS

Abstract:One of the most recent techniques for the diagnosis of EP (early pregnancy) in cattle on the farm is B-mode ultrasonography. Under field conditions, acceptable results may be achieved with ultrasonography from days 25 to 30 post-AI. The reliability of the test greatly depends on the frequency of the transducer used, the skill of the examiner, the criterion used for a positive PD (pregnancy diagnosis) and the position of the uterus in the pelvic inlet. Pregnancy protein assays (PAG, PSPB) may provide an alternative method to ultrasonography for determining EP or LEM/EFM (late embryonic/early foetal mortality) in the cow. Although early pregnancy factor is the earliest specific indicator for fertilization, its detection is entirely dependend on the use of the RIT (rosette inhibition test), therefore its use in the field needs further inventions. Preventive pharmaceutical treatments with hCG (human chorionic gonadotropin), GnRH (gonadotropin realising hormone), PRID (progesterone-releasing intravaginal device) or CIDR (controlled internal drug release) inserts at different time periods at or post-AI may have some benefit in decreasing PL (pregnancy loss), however further examinations are warranted to determine how and when these treatments may influence PL in the field.

“…The pregnancy-associated protein, early pregnancy factor (EPF), was detected originally by its ability to bind to lymphocytes, and in so doing alter their reaction in the rosette inhibition test (1,2). Further investigations indicated that EPF has immunosuppressive activity, suppressing the adoptive transfer of contact sensitivity from sensitized mice to naive syngeneic mice (3,4).…”

Section: Introductionmentioning

confidence: 99%

Genetically‐restricted effector molecules released by human lymphocytes in response to early pregnancy factor

Rolfe

Quinn²,

Athanasas³

et al. 1989

Immunol Cell Biol

Self Cite

SummaryThe binding of early pregnancy factor (EPF) to lymphocytes stimulates the release of soluble effector molecules. Studies in mice have shown that it is these factors rather than EPF as such which are inhibitory in the T cell-dependent reactions, the adoptive transfer of contact sensitivity and the rosette inhibition test. Two factors have been identified: mEPF-Si (Mr ~15 000) is major histocompatibility complex (MHC)-restricted while mEPF-S2 (Mr ~55 000) is restricted to a locus (or loci) outside the MHC. In the present paper, evidence is presented which shows that EPF also induces the release of soluble mediators from human lymphocytes. With the rosette inhibition test two factors have been detected, both of similar size and genetic restriction to those described previously in the mouse. One factor, designated hEPF-Si (Mr 14-18 000), is human lymphocyte antigen (HLA)-restricted and the other, hEPF-S2 (Mr 50-60 000), appears to be restricted to a locus (or loci) outside the HLA complex.