La Rocca Claudia, Carbone Fortunata, Longobardi Salvatore, Matarese Giuseppe
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via Pansini 5, 80131 Napoli, Italy; Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), via Pansini 5, 80131 Napoli, Italy.
Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), via Pansini 5, 80131 Napoli, Italy.
Immunol Lett. 2014 Nov;162(1 Pt A):41-8. doi: 10.1016/j.imlet.2014.06.013. Epub 2014 Jul 1.
Establishment and maintenance of pregnancy represents a challenge for the maternal immune system since it has to defend against pathogens and tolerate paternal alloantigens expressed in fetal tissues. Regulatory T (Treg) cells, a subset of suppressor CD4(+) T cells, play a dominant role in the maintenance of immunological self-tolerance by preventing immune and autoimmune responses against self-antigens. Although localized mechanisms contribute to fetal evasion from immune attack, in the last few years it has been observed that Treg cells are essential in promoting fetal survival avoiding the recognition of paternal semi-allogeneic tissues by maternal immune system. Several functional studies have shown that unexplained infertility, miscarriage and pre-clampsia are often associated with deficit in Treg cell number and function while normal pregnancy selectively stimulates the accumulation of maternal forkhead-box-P3(+) (FoxP3(+)) CD4(+) Treg cells with fetal specificity. Some papers have been reported that the number of Treg cells persists at elevated levels long after delivery developing an immune regulatory memory against father's antigens, moreover these memory Treg cells rapidly proliferate during subsequent pregnancies, however, on the other hand, there are several evidence suggesting a clear decline of Treg cells number after delivery. Different factors such as cytokines, adipokines, pregnancy hormones and seminal fluid have immunoregulatory activity and influence the success of pregnancy by increasing Treg cell number and activity. The development of strategies capable of modulating immune responses toward fetal antigens through Treg cell manipulation, could have an impact on the induction of tolerance against fetal antigens during immune-mediated recurrent abortion.
妊娠的建立和维持对母体免疫系统来说是一项挑战，因为它必须抵御病原体并耐受胎儿组织中表达的父系同种异体抗原。调节性T（Treg）细胞是抑制性CD4(+) T细胞的一个亚群，通过防止针对自身抗原的免疫和自身免疫反应，在维持免疫自我耐受中起主导作用。尽管局部机制有助于胎儿逃避免疫攻击，但在过去几年中人们观察到，Treg细胞对于促进胎儿存活至关重要，可避免母体免疫系统识别父系半同种异体组织。多项功能研究表明，不明原因的不孕、流产和先兆子痫通常与Treg细胞数量和功能缺陷有关，而正常妊娠则选择性地刺激具有胎儿特异性的母体叉头框P3(+)（FoxP3(+)）CD4(+) Treg细胞的积累。一些论文报道，Treg细胞数量在分娩后很长时间内持续维持在较高水平，形成对父亲抗原的免疫调节记忆，此外，这些记忆性Treg细胞在随后的妊娠期间迅速增殖，然而，另一方面，有多项证据表明分娩后Treg细胞数量明显下降。细胞因子、脂肪因子、妊娠激素和精液等不同因素具有免疫调节活性，并通过增加Treg细胞数量和活性来影响妊娠的成功。通过操纵Treg细胞来调节针对胎儿抗原的免疫反应的策略的开发，可能会对免疫介导的复发性流产期间诱导对胎儿抗原的耐受性产生影响。
