Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero

By Jeff E. Mold, J. Michaëlsson, T. Burt, M. Muench, K. Beckerman, M. Busch, Tzong-Hae Lee, D. Nixon, J. McCune. Science, 2008

847 citations recorded by the source corpus.

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7bcfff381e4e83fae14a8f3c3e79f7b680327b2d

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Citations in the corpus

• Stereotypic Immune System Development in Newborn Children (2018, background): “Recent results indicate that the developing immune system in prenatal life is fully functional, but actively suppressed (Elahi et al., 2013; Zhang et al., 2017) and that regulatory T cells are important mediators of this suppression (McGovern et al., 2017; Mold et al., 2008).”
• Human T cell development, localization, and function throughout life (2018, background): “The early establishment of Treg cells in utero is followed by elevated levels in early life with to 10– 30% of all CD4+T cells in blood, lymphoid tissue, and mucosal sites being Treg cells compared to less than 5% in adults (Mold et al., 2008; Thome et al., 2016a).”
• Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns (2010, background): “(3) recently reported that vaginal communities not dominated by lactobacilli but by strictly anaerobic bacteria were common in healthy black and Hispanic women.”
• Overview of the Immune Response (2003, background): “Additionally, lymphocytes in these secondary lymphoid tissues were poorly activated when exposed to an allogeneic stimulus.(119) These high numbers of Treg cells returned to normal shortly after delivery.”
• The multifaceted role of CD4+ T cells in the regulation of CD8+ T cell memory maturation (2015, positive): “Compulsory early developmen­ tal exposure to genetically foreign maternal antigens primes in offspring sustained tolerance to non­inherited maternal antigens and persistently increased T Reg cells with specificity to these genetically foreign maternal antigens 54–56 .”
• IgG Placental Transfer in Healthy and Pathological Pregnancies (2011, background): “It has been demonstrated that in the in utero environment, CD4+CD25hiFoxp3+ regulatory T cells dominate the fetal circulation, suppressing reactivity to noninherited maternal antigens [14] and possibly promoting a generally suppressive environment.”