Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
Placenta. 2010 Sep;31(9):796-802. doi: 10.1016/j.placenta.2010.06.019. Epub 2010 Aug 2.
Regulatory T cells (Tregs) support pregnancy maintenance by suppressing placental inflammation, while diminished Treg function may accompany reproductive failure. Experimental FIV infection frequently results in vertical transmission and increased pregnancy failure in the cat. The mechanism of reproductive compromise is unknown. We hypothesized that FIV infection alters endometrial Treg population dynamics and function, potentiating vertical transmission and reproductive failure. RNA collected from early and late gestation reproductive tissue and fetuses from FIV infected and control cats was probed for expression of FIV gag and Treg markers CD25, FOXP3, and CTLA4, using real time reverse-transcriptase (RT)-PCR. Frequent placental and fetal infection and reproductive failure were detected at early and late pregnancy. Expression of FOXP3 and CTLA4 was higher in early gestation tissues from control cats. FIV infection significantly reduced expression of FOXP3 and CTLA4 at early, but not late pregnancy. At late pregnancy, CTLA4 was expressed to higher levels in infected tissues. The number of tissues with decreased co-expression of FOXP3 and CTLA4 was significant in infected cats at early pregnancy. No significant changes in CD25 expression occurred between FIV-infected and control animals at early or late pregnancy. Differences in Treg marker expression were not significant between viable and non-viable pregnancies in infected cats. The detection of Treg markers in these feline tissues provides the first evidence of feline endometrial Tregs and suggests that such cells diminish as pregnancy progresses. These cells may be depleted or rendered less functional by viral infection, but understanding their role in pregnancy requires further study.
调节性 T 细胞(Tregs)通过抑制胎盘炎症来支持妊娠维持,而 Treg 功能的降低可能伴随着生殖失败。实验性 FIV 感染常导致猫垂直传播和妊娠失败增加。生殖失败的机制尚不清楚。我们假设 FIV 感染改变了子宫内膜 Treg 群体动力学和功能,从而增强了垂直传播和生殖失败的可能性。从 FIV 感染和对照猫的早期和晚期妊娠生殖组织和胎儿中收集 RNA,使用实时逆转录(RT)-PCR 探测 FIV gag 和 Treg 标记物 CD25、FOXP3 和 CTLA4 的表达。在早期和晚期妊娠时频繁检测到胎盘和胎儿感染以及生殖失败。在对照猫的早期妊娠组织中,FOXP3 和 CTLA4 的表达更高。FIV 感染显著降低了早期妊娠时 FOXP3 和 CTLA4 的表达,但晚期妊娠时则没有。在晚期妊娠时,感染组织中 CTLA4 的表达水平更高。在感染猫的早期妊娠中,FOXP3 和 CTLA4 共表达减少的组织数量显著增加。在早期或晚期妊娠时,FIV 感染和对照动物之间的 CD25 表达没有明显变化。在感染猫中,存活和非存活妊娠之间 Treg 标记物的表达差异不显著。这些猫科动物组织中 Treg 标记物的检测首次提供了猫子宫内膜 Tregs 的证据,并表明这些细胞随着妊娠的进展而减少。这些细胞可能因病毒感染而被耗尽或功能降低,但要了解它们在妊娠中的作用还需要进一步研究。