REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

Abstract

Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010T‐helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)‐β and interleukin (IL)‐10 or by cell‐to‐cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms.

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

“…The present study, however, is to our knowledge the first to show a direct impact of MDSCs on T cell polarization in humans. During pregnancy, a polarization toward Th2 response has long been considered as a main mechanism of tolerance induction toward the fetus (8,9,60,61). Although the lack of Th2 cytokines does not necessarily affect normal pregnancy progress (62), a predominance of Th1-type immunity and a reduced expression of Th2 cytokines may result in recurrent spontaneous abortion and preeclampsia (28,29).…”

“…One way by which they are involved in successful pregnancy maintenance is a change in the T cell cytokine profile toward a predominance of Th2 cytokines, which may protect against fetal rejection by maternal Th1 cells (8,9). Little is known about the mechanisms regulating T cell function during pregnancy.…”

L’implantation embryonnaire

“…Ces facteurs sont impliqués dans la régulation de la réponse immunitaire, l'induction d'une tolérance immunitaire, le contrôle de l'angiogenèse locale et de l'immunotrophisme (voir note 2). Il faut également préciser que la présence d'hCG à l'interface embryo-maternelle intervient directement dans l'équilibre Th1/Th2 et la sécrétion de cytokines Th2 [50] qui contribuent à la tolérance immunitaire et à la création d'un environnement favorable à la croissance et au développement du foetus [51,52]. Mais, au-delà de l'équilibre Th1/Th2 et de ses limites pour expliquer le succès ou l'échec de la grossesse, l'hCG joue également un rôle dans le recrutement des cellules Treg dont on sait maintenant qu'ils sont des acteurs clés de la tolérance immunitaire locale [30,52] et dont l'équilibre avec les cellules Th17 (effectrices pro-inflammatoires) semble la réceptivité maternelle et l'implantation embryonnaire.…”

EFFECTS OF γс-CYTOKINES (IL-2, IL-7 AND IL-15) UPON IN VITRO MATURATION AND DIFFERENTIATION OF CD4⁺CD45RО⁺/CD8⁺CD45RО⁺ T CELLS

“…В современной литературе вопрос об этапности дифференцировки Т-лимфоцитов до конца не изучен. Рассматривается несколько моделей формирования клеток памяти из «наи-вных» предшественников [2,7,9,10,25,31,36]. Так, в модели независимой дифференцировки предполагается, что Т СМ и Т EM могут возникать независимо друг от друга, на основе стохастиче-ского прайминга наивных Т-лимфоцитов или в зависимости от условий их стимуляции [10].…”