Asian Journal of Immunology

Background: Immune tolerance is established between the foetus and the mother in normal pregnancies. However, this tolerance may be breached, resulting in undesired pregnancy outcomes such as spontaneous abortion, foetal anomalies, and maternal complications. Reported studies suggest a potential link between immune response and unplanned pregnancy termination. A comprehensive understanding of immune responses in pregnancy loss harbours the potential to control the associated mechanisms. 

Objective: This review synthesised existing studies on T cell exhaustion (TCE) in spontaneous abortion and pregnancy complications.

Methodology: A comprehensive database search from Scopus, Google Scholar, PubMed, and Web of Science identified 21 eligible studies that reported original data on spontaneous abortion and pregnancy complications and TCE.

Results: The review has shown that TCE is common in spontaneous abortion, characterised by the upregulation of inhibitory receptors and a suboptimal or lack of T-cells to perform their normal functions, such as proliferation, cytokine production, and cytotoxicity. Decreased expression of PD-1, LAG-3 and Tim-3 may contribute to an enhanced inflammatory response. Increased proportions of Th1 and Th17 cells are associated with pro-inflammatory responses and decreased immune regulatory function, resulting from altered PD-1/PD-L1 expression, which may contribute to pregnancy loss. Decreased anti-inflammatory cytokines (TGF-β1, IL-10, and IL-4) promote an imbalanced homeostasis, which can lead to pregnancy loss. These anomalies are partly anchored on chronic antigen exposure, oxidative stress, and hormonal changes, phenomena frequently associated with recurrent spontaneous abortion or poor pregnancy outcomes. 

Conclusion: Optimal modulation of immune response to control TCE may prevent or minimise the occurrence of spontaneous abortion and promote successful pregnancies.