妊娠中の母体調節性T細胞の起源と抗原特異性を探る

Exploring the Origin and Antigenic Specificity of Maternal Regulatory T Cells in Pregnancy.

• Soo Hyun Ahn
• Sean L Nguyen
• Margaret G Petroff

抄録

妊娠の成功は、母体と胎児の界面での母体調節性T細胞（T）による反応性エフェクターT細胞の抑制によって部分的に決定されます。研究の大規模な領域は、トランスジェニックマウスモデルとヒトサンプルを使用して、末梢誘導T（pT）分布と分化の制御に焦点を当てているが、胸腺（tT）由来のTの役割に焦点を当てた研究、および母体胎児の耐性における中枢性耐性の潜在的な役割はあまり探索されていません。胎児のゲノムは、組織特異的な抗原と父方由来の抗原の両方で構成されており、いずれかの抗原への母方の免疫寛容性のブレークは、不利な妊娠の結果につながる可能性があります。胎児と胎盤に高度に制限されている抗原を含む"自己"抗原は、自己免疫調整剤（Aire）の制御下で髄質胸腺上皮細胞によって遊離的に発現している、これは、これらの抗原に向かって特異的になるようにtTT T細胞受容体（TCR）レパートリーを歪ませる。このように、このように、私たちは、このような研究を行うことができます。

Successful pregnancy outcome is partially determined by the suppression of reactive effector T cells by maternal regulatory T cells (T) at the maternal-fetal interface. While a large area of research has focused on the regulation of peripherally-induced T (pT) distribution and differentiation using transgenic mouse models and human samples, studies focusing on the role of T derived from the thymus (tT), and the potential role of central tolerance in maternal-fetal tolerance is less explored. The genome of the fetus is composed of both the tissue-specific and paternally-inherited antigens, and a break in maternal immune tolerance to either antigen may result in adverse pregnancy outcomes. Notably, "self"-antigens, including antigens that are highly restricted to the fetus and placenta, are promiscuously expressed by medullary thymic epithelial cells under the control of Autoimmune Regulator (Aire), which skews the tT T cell receptor (TCR) repertoire to be specific toward these antigens. T that circulate in mothers during pregnancy may be comprised of T that stem from the thymus as well as those induced in the periphery. Moreover, despite a wealth of research dedicated to elucidating the function of T in maternal-fetal tolerance, little is understood about the origin of these cells, and whether/how tT may contribute. Investigation into this question is complicated by the absence of reliable markers to distinguish between the two. In this review, we discuss how distinct types of fetal/placental antigens may determine the generation of different subtypes of T cells in the mother, and in turn how these may promote maternal tolerance to the fetus in pregnancy.

Copyright © 2020 Ahn, Nguyen and Petroff.