4.5 Article

Human labour is associated with altered regulatory T cell function and maternal immune activation

Journal

CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 199, Issue 2, Pages 182-200

Publisher

OXFORD UNIV PRESS
DOI: 10.1111/cei.13384

Keywords

reproductive immunology; tolerance; suppression; anergy; Toll-like receptors (TLRs); regulatory T cells

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Funding

  1. National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC) [1167073]

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During human pregnancy, regulatory T cell (T-reg) function is enhanced and immune activation is repressed allowing the growth and development of the feto-placental unit. Here, we have investigated whether human labour is associated with a reversal of the pregnancy-induced changes in the maternal immune system. We tested the hypothesis that human labour is associated with a decline in T-reg function, specifically their ability to modulate Toll-like receptor (TLR)-induced immune responses. We studied the changes in cell number, activation status and functional behaviour of peripheral blood, myometrial (myoMC) and cord blood mononuclear cells (CBMC) with the onset of labour. We found that T-reg function declines and that T-reg cellular targets change with labour onset. The changes in T-reg function were associated with increased activation of myoMC, assessed by their expression of major histocompatibility complex (MHC) class II molecules and CBMC inflammatory cells. The innate immune system showed increased activation, as shown by altered monocyte and neutrophil cell phenotypes, possibly to be ready to respond to microbial invasion after birth or to contribute to tissue remodelling. Our results highlight changes in the function of the adaptive and innate immune systems that may have important roles in the onset of human labour.

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