The Role of Subpopulations of Cd8+ T Lymphocytes in the Development of Pregnancy

Abstract

At the present time, a broad spectrum of CD8+ T lymphocyte subsets is revealed, including naïve cells, memory cells and regulatory subpopulations. Along with cells with high cytolytic activity, some subsets with marked regulatory activity were found there. Each subpopulation is characterized by a set of produced mediators, surface and intracellular markers allowing to suggest their differential in vivo functional activity. The present review article proposes a classification of CD8+ Т cells which takes into account their morphological and functional features. According to conventional view, the CD8+ Т lymphocytes is a cell population exhibiting high cytotoxic ability which is of critical significance in pregnancy, under the conditions of semi-allogenic fetal cell invasion into the endometrium. The fraction of CD8+ T cells is rather high in decidual structures. The review discusses the known mechanisms of differentiation regulation, selective migration and activity of CD8+ T cells in decidual membrane and placenta in the course of pregnancy. Perforine and granzyme are the main cytotoxicity factors of CD8+ Т cells. IL-2, IL-5, IL-13, IFNγ, IL-17, TGF-β and IL-10 cytokines are considered regulatory mediators of CD8+ cells. To induce the effector properties of CD8+ T cells, an antigenic stimulation is required, which is provided by interactions between the CD8+ Т cells and activated CD4+ Т cells or dendritic cells, cytokine effects. Specific differentiation of the CD8+ T cells is determined by differences in microenvironvent. In the course of pregnancy, accumulation of CD8+ Т cells is observed in decidual membrane, but their phenotype and functional properties differ from CD8+ Т cells in peripheral blood. At present time, the mechanisms of selective CD8+ T cell migration to decidual membrane are studied. These events are suggested to be mediated by means of CXCR3 and CCR5 chemokine receptors, IL-6 and IL-15 cytokines. The features of CD8+ Т cell activities, and production of some cytokines, e.g., CSF2, IFNγ, IL-1β, IL-2, IL-6, IL-8,IL-10, IL-12 and TNFα in decidual membrane and is of critical significance for effective invasion of trophoblast cells. In turn, the trophoblast and placental cells promote development of regulatory CD8+ Т lymphocytes in decidual membrane, being able to induce CD8+ T cell apoptosis in decidual membrane. Hence, interaction between the maternal CD8+ T cells and trophoblast in the area of uterine-placental contact is an important link during development of immunological tolerance in the maternal/fetal system.