Female reproductive health is strongly associated with healthy vaginal microbiota, which is thought to be ensured by the dominance of certain Lactobacillus species. Lactobacilli control the vaginal microenvironment through several factors and mechanisms. One of them is their ability to produce hydrogen peroxide (H₂O₂). The role of Lactobacillus-derived H₂O₂ in the vaginal microbial community has been intensively investigated in several studies with many designs. However, results and data are controversial and challenging to interpret in vivo. Defining the underlying mechanisms responsible for a physiological vaginal ecosystem is crucial since it could directly affect probiotic treatment attempts. This review aims to summarize current knowledge on the topic, focusing on probiotic treatment possibilities.

NKT cells represent a small but significant immune cell population as being a part of and bridging innate and adaptive immunity. Their ability to exert strong immune responses via cytotoxicity and cytokine secretion makes them significant immune effectors. Since pregnancy requires unconventional maternal immunity with a tolerogenic phenotype, investigation of the possible role of NKT cells in materno-fetal immune tolerance mechanisms is of particular importance. This review aims to summarize and organize the findings of previous studies in this field. Data and information about NKT cells from mice and humans will be presented, focusing on NKT cells characteristics during normal pregnancy in the periphery and at the materno-fetal interface and their possible involvement in female reproductive failure and pregnancy complications with an immunological background.

Pregnancy is an immunological enigma where paternal antigens are present at the fetomaternal interface. What regulates the local immunotolerance, which is necessary to prevent rejection of the conceptus, is still under strong investigation. Gamma/delta T cells are believed to play a role in the local regulation of this immunotolerance towards the semiallogenic fetus. Gamma/delta T cells from the uterus and spleen of pregnant and nonpregnant mice were analyzed by flow cytometry. We confirmed that the rate ofγδT cells in the decidua increases during murine pregnancy and half of decidualγδT cells are CD4+. Furthermore, we found a unique association of CD4 or CD8 coreceptor expression with theirγδTCR intensity, where in all investigated groups CD4- or CD8-positiveγδT cells seemed principally to beγδTCRdim. In addition, compared to peripheralγδT lymphocytes, a greater proportion of decidualγδT cells expressed the cytotoxic marker CD107a and markers of Th1 or Th2 polarization (TIM-3, TIM-1), where decidualγδTCRbright cells were characterized by high TIM-3 and TIM-1 receptor expression. On the other hand, no difference in the expression of CD160, a receptor with dual function affecting cytotoxicity and T cell inhibition, was detected. Within lymphocytes expressing CD107a, TIM-1, or CD160, the rate ofγδT cells was significantly higher in the decidua. According to our results, cytotoxic potential of decidualγδTCRbright cells could be regulated by TIM-3 ligation, while the TIM-1 receptor seems to be able to influence the Th1-Th2 balance at the fetomaternal interface. These mechanisms could play a part in the active maternal immunotolerance towards the fetus, allowing an efficient protection against pathogens during healthy murine pregnancy.

During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother’s body. The trophoblast’s unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.