Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation

Abstract

CD8+ T cells recognize non-self antigen by MHC class I molecules and kill the target cells by the release of proinflammatory cytokines such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Our group previously reported an increase of CD8+ T‐cell trafficking in the placenta with exposure to Lipopolysaccharides (LPS). CD8+ cytotoxic T cells have been classified into distinct subsets based upon cytokine production: Tc1 cells produce IFN-γ, Tc2 cells produce interleukin 4 (IL-4). Accordingly, the purpose of this research is to analyze the subsets of placenta CD8+ T cells. We hypothesized that LPS injection would induce a change of properties of CD8+ T cell and Tc1/Tc2 ratio. We investigated the subsets of CD8+ T cell infiltration to placenta and their specific function in response to LPS-induced inflammation in a mouse model. At embryonic (E) day 17, pregnant CD-1 dams received an intrauterine injection of 25 µg LPS in100 μl PBS or 100 μl of PBS only. Flow cytometry was used to quantify CD8+ T cells, evaluate the phenotype and subtypes, and detect markers of Tc1 and Tc2 cells in placenta, at 6 hours and 24 hours post injection (hpi). Intracellular staining and flow cytometry were performed to characterize cytokines produced by CD8+ T cells. Standard statistical analysis were employed. After 6 and 24 hours of LPS injection, total CD8 T cells increased (P<0.05). Tc1 cells expanded (P<0.05) in LPS-treated dams compared with the PBS group. The Tc1/Tc2 ratio was significantly higher in the LPS group than the PBS group (P<0.05). The expression of TNF-α and IFN-γ were increased in LPS group both at 6hpi and 24 hpi (P<0.05). We identified functional placental CD8+ T cell subtypes and found a significant increase ratio of Tc1/Tc2. Following IUI, CD8+ T cells induced inflammatory response in the placenta primarily via the production of Type 1 cytokines such as IFN-γ and TNF-α. We have provided evidence of a Tc1-bias response and cytokines in the mouse model of IUI.

Dendrimer-Based N-Acetyl Cysteine Maternal Therapy Ameliorates Placental Inflammation via Maintenance of M1/M2 Macrophage Recruitment

“…At 3hpi and 6hpi, CD45 + leukocyte infiltrates in the placenta were significantly increased in LPS + PBS group compared to PBS + PBS group, while maternal treatment of DNAC significantly decreased CD45 + leukocytes infiltration in LPS + DNAC group compared to LPS + PBS group (Figure 2B, p < 0.05). Similarly, as our prior study demonstrated, CD45 + leukocyte infiltration in placenta increased with LPS-exposure at 6hpi of E17 (Lei et al, 2017;Liu et al, 2021). At 12hpi, CD45 + leukocytes infiltration in the placenta did not show any significant difference between groups (Figure 2B).…”

“…The maternal-fetal interface supports multiple cellular immune systems comprising adaptive immune T cells and homeostatic innate immune cells such as macrophages. T cells have been shown to participate in placental pathological inflammation during pregnancy (Lee et al, 2011;Arenas-Hernandez et al, 2019;Liu et al, 2021). We proved that DNAC prevents CD3 + /CD45 + cells increased by LPS-induced placental inflammations, but free NAC treatment does not.…”

“…CD-1 pregnant dams from Charles River were used for this study. Pregnant dams were subjected to a well-established model of IUI as per a previously described protocol on embryonic day 17 (E17) (Burd et al, 2010;Elovitz et al, 2011;Dada et al, 2014;Lei et al, 2017;Lei et al, 2018;Liu et al, 2021;Na et al, 2021). Briefly, mice were anesthetized with isoflurane (Baxter # NDC 10019-360-60) before undergoing a mini-laparotomy.…”

Recent progress and perspectives on the relationship between hyperuricemia and periodontitis

“…A significantly increased number of Type 1 CD8+ T cells and the ratio of Type 1 CD8+ T cells to Type 2 CD8+ T cells were detected (89). Simultaneously, more pro-inflammatory cytokines and further destructions in the tissue that indicated enhanced immune and inflammatory responses may induce lasting chronic inflammation (89). Of note, Chen et al found the incidence rate of periodontitis in the subjects with gout was significantly higher than that in the comparison cohort, while the risk of periodontitis in gout patients using colchicine was significantly lower (90).…”

“…Liu et al. demonstrated that the Type 1 CD8+ T cells were the main participants in the inflammatory cytotoxic responses when exposed to LPS ( 89 ). A significantly increased number of Type 1 CD8+ T cells and the ratio of Type 1 CD8+ T cells to Type 2 CD8+ T cells were detected ( 89 ).…”