Peripheral Blood NK Cell Cytotoxicities are Negatively Correlated with CD8+ T Cells in Fertile Women but not in Women with a History of Recurrent Pregnancy Loss

2012 ◽  
Vol 68 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Ji Hee Yoo ◽  
Joanne Kwak-Kim ◽  
Ae-Ra Han ◽  
Hyunkyong Ahn ◽  
Sun-Hwa Cha ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Nk Cell ◽  
History Of ◽  
Fertile Women

scholarly journals Systemic Characterization of Novel Immune Cell Phenotypes in Recurrent Pregnancy Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Liu ◽  
Xin-Xiu Lin ◽  
Xiao-Bo Huang ◽  
Dong-Hui Huang ◽  
Su Song ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Immune Cell Subsets ◽  
History Of ◽  
Cell Phenotypes

Recurrent pregnancy loss (RPL) is a disturbing disease in women, and 50% of RPL is reported to be associated with immune dysfunction. Most previous studies of RPL focused mainly on the relationship between RPL and either T cells or natural killer (NK) cells in peripheral blood and the decidua; few studies presented the systemic profiles of the peripheral immune cell subsets in RPL women. Herein, we simultaneously detected 63 immune cell phenotypes in the peripheral blood from nonpregnant women (NPW), women with a history of normal pregnancy (NP) and women with a history of RPL (RPL) by multi-parameter flow cytometry. The results demonstrated that the percentages of naïve CD4+ T cells, central memory CD4+ T cells, naïve CD8+ T cells, mature NK cells, Vδ1+ T cells and the ratio of Vδ1+ T cells/Vδ2+ T cells were significantly higher in the RPL group than those in the NPW and NP groups, whereas the percentages of terminal differentiated CD4+ T cells, effective memory CD4+ T cells, immature NK cells and Vδ2+ T cells were significantly lower in the RPL group than those in the NPW and NP groups. Interestingly, we found that peripheral T helper (TPH) cells were more abundant in the NPW group than in the NP and RPL groups. Moreover, the percentage of Vδ2+PD-1+ gamma-delta (γδ) T cells was extremely high, above the 95th percentile limit, in the NP group compared with the NPW and RPL groups, which has never been reported before. In addition, we also determined the 5th percentile lower limit and 95th percentile upper limit of the significantly changed immunological parameters based on the files of the NPW group. Taken together, this is the first study to simultaneously characterize the multiple immune cell subsets in the peripheral blood at a relatively large scale in RPL, which might provide a global readout of the immune status for clinicians to identify clinically-relevant immune disorders and guide them to make clear and individualized advice and treatment plans.

scholarly journals Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

2021 ◽  
Vol 10 (21) ◽  
pp. 5086
Author(s):  
Monika Kniotek ◽  
Aleksander Roszczyk ◽  
Michał Zych ◽  
Małgorzata Wrzosek ◽  
Monika Szafarowska ◽  
...  
Keyword(s):  
Nk Cells ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Nk Cell ◽  
Cell Activity ◽  
No Synthase ◽  
Angiogenic Factors ◽  
Nk Cell Activity ◽  
Culture Supernatants ◽  
Fertile Women

In our previous study, we showed that sildenafil citrate (SC), a selective PDE5A blocker, modulated NK cell activity in patients with recurrent pregnancy loss, which correlated with positive pregnancy outcomes. It was found that NK cells had a pivotal role in decidualization, angiogenesis, spiral artery remodeling, and the regulation of trophoblast invasion. Thus, in the current study, we determined the effects of SC on angiogenic factor expression and production, as well as idNK cell activity in the presence of nitric synthase blocker L-NMMA. Methods: NK cells (CD56+) were isolated from the peripheral blood of 15 patients and 15 fertile women on MACS columns and cultured in transformation media containing IL-15, TGF-β, and AZA—a methylation agent—for 7 days in hypoxia (94% N2, 1% O2, 5% CO2). Cultures were set up in four variants: (1) with SC, (2) without SC, (3) with NO, a synthase blocker, and (4) with SC and NO synthase blocker. NK cell activity was determined after 7 days of culturing as CD107a expression after an additional 4h of stimulation with K562 erythroleukemia cells. The expression of the PDE5A, VEGF-A, PIGF, IL-8, and RENBP genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes and ELISA was used to measure the concentrations of VEGF-A, PLGF, IL-8, Ang-I, Ang-II, IFN–γ proteins in culture supernatants after SC supplementation. Results: SC downregulated PDE5A expression and had no effect on other studied angiogenic factors. VEGF-A expression was increased in RPL patients compared with fertile women. Similarly, VEGF production was enhanced in RPL patients’ supernatants and SC increased the concentration of PIGF in culture supernatants. SC did not affect the expression or concentration of other studied factors, nor idNK cell activity, regardless of NO synthase blockade.

WED 186 Effect of cladribine tablets on immune cells in patients with ms

2018 ◽  
Vol 89 (10) ◽  
pp. A26.2-A26
Author(s):  
Olaf Stuve ◽  
Per Soelberg-Sorensen ◽  
Gavin Giovannoni ◽  
Thomas Leist ◽  
Yann Hyvert ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Active Treatment ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Peripheral Blood Lymphocytes ◽  
Treatment Groups ◽  
Absolute Lymphocyte Counts ◽  
Temporal Profiles

BackgroundCladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in patients with early (ORACLE-MS) and relapsing MS (CLARITY/CLARITY-Extension).ObjectiveEvaluate B, T lymphocyte and natural killer (NK) cell profiles after CT administration in ORACLE-MS, CLARITY and CLARITY-Extension.MethodsLongitudinal evaluation of peripheral blood lymphocytes was conducted for patients receiving the CT (either part of the initial 3.5 mg/kg active treatment groups or placebo switched to active treatment). Absolute lymphocyte counts (ALC) and subtype dispositions were evaluated at baseline, and Weeks 5, 13, 24, 48.ResultsBaseline distributions of ALC and temporal profiles of CD19+ B and CD4+ and CD8+ T lymphocytes were generally consistent across studies. Rapid reductions were observed for CD19+ B cells (~75% reduction; Week 5), with nadirs at Week 13 (~80% reduction). Reconstitution of CD19+ B cells towards baseline occurred from Week 24–48. Lesser, discontinuous reductions also occurred for CD4+ and CD8+ T cells that had not fully returned to baseline by Week 48. CD16+/CD56+ NK cells were transiently reduced with CT, with recovery evident at Weeks 24 (29%) and 48 (23%).ConclusionsCT3.5 achieved early, discontinuous reduction of peripheral blood B cells, with rapid reconstitution towards baseline; a moderate, discontinuous reduction of T cells; and early, transient NK cell reductions.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_LymphBTNKCell.pdf

scholarly journals Diagnostic significance of assessing peripheral natural killer cells in women with recurrent pregnancy loss

2021 ◽  
Vol 15 (1) ◽  
pp. 61-69
Author(s):  
K. E. Gotsiridze ◽  
N. P. Kintraya
Keyword(s):  
Pregnant Women ◽  
Peripheral Blood ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Comparison Group ◽  
Nk Cell ◽  
Complete Blood Count ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

Aim: to assess peripheral blood NK cell (pNK) counts in women with recurrent pregnancy loss.Materials and Methods. There were examined 102 women: 28 non-pregnant (immediately after repeatedly terminated pregnancy, group IA) and 34 pregnant women with history of previous recurrent pregnancy loss (group IB). Control and comparison groups were consisted of healthy women lacking any recorded miscarriage: 20 non-pregnant (group IIA) and 20 pregnant women (group IIB), respectively. Along with assessing complete blood count range, all subjects were analyzed percentage of pNK cell CD16bright(+) CD56dim(-) cytotoxic phenotype by using fluorescence microscopy as well as level of cytokines IL-2, IL-6, IL-10, tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-γ) using ELISA.Results. It was found that the level of NK cell cytotoxic phenotype - percentage of CD16+CD56- was elevated in both groups: groups: group IA - 36.5 % collared with the control group IIA - 27.5% (р < 0.05); in group IB up to 37.0 %, in comparison group IIB - 27.4% (р < 0.01). It was further corroborated by increased level of serum cytokine IL-6 IL-6 comprising in group IA vs. IIA - 28.5 pg/ml vs. 14.2 pg/ml (р < 0.01) as well as in group IB vs. IIB up to 16.7 pg/ml vs. 12.2 pg/ml (р < 0.01), respectively. However, level of serum IL-2 and IL-10 did not significantly differ in all groups examined. Interestingly, level of VEGF in subjects aged 21-30 years was elevated: in non-pregnant (group IA) vs. control (group IIA) - up to 548.5 pg/ml vs. 310.8 pg/ml (р < 0.01); pregnant women (IB) vs. comparison group (IIB) - insignificantly elevated up to 476.1 pg/ml vs. 381.5 pg/ml, respectively. In contrast, no significant changes were observed in 31-40-year group. Concentration of IFN-γ in group IA vs. control group (IIA) was increased up to 9.2 pg/ml vs.8.64 pg/ml; group IB vs. comparison group - up to 8.36 pg/ml vs. 7.56 pg/ml, respectively.Conclusion. Elevated percentage of cytotoxic CD16+CD56- NK cells in peripheral blood results in imbalance of immune-related parameters that directly correlated with increased serum level of IL-2, IL-6, TNF-α that may alter maternal immune tolerance to the fetus and subsequently resulting in recurrent pregnancy loss. Hence, the aforementioned data may be used as diagnostic and prognostic criteria in recurrent pregnancy losses.

571 ANV419 is a novel CD122-selective IL-2/anti-IL-2 antibody fusion protein with potent CD8 T cell and NK cell stimulatory function in vitro and in vivo

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A605-A605
Author(s):  
Christoph Huber ◽  
Andreas Katopodis ◽  
Barbara Branetti ◽  
Jean-Michel Rondeau ◽  
Simone Popp ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Binding Site ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Nk Cell ◽  
High Dose

BackgroundANV419 is a uniquely engineered IL-2 fusion to an antibody selectively blocking the IL-2 receptor alpha (CD25) binding site. It signals selectively through the CD122/CD132 dimeric IL-2 receptor and stimulates the proliferation of CD8 T cells and NK cells while avoiding the proliferation of immunosuppressive regulatory T cells (Treg). Therefore, ANV419 has the potential to substantially separate targeted T-cell and NK cell proliferation and anti-tumor responses from the dose limiting toxicities of recombinant IL-2 (aldesleukin). ANV419 has antibody like stability and behavior and is currently in late preclinical development for tumor immunotherapy.MethodsThe crystal structure of ANV419 has been solved and its binding affinity to CD25 and CD122 has been determined. In vitro and in vivo studies, including pharmacodynamics and toxicity, have been performed in rodents and non-human primates. The ability of ANV419 to inhibit tumor growth has been studied in mouse syngeneic models.ResultsStructural analysis demonstrates that the CD25 binding site of IL-2 is completely blocked in ANV419 while the CD122/CD132 sites are available for binding. As a result, ANV419 lacks CD25 binding activity but retains IL-2 receptor beta (CD122) affinity comparable to native IL-2. In human peripheral blood monocyte cultures, ANV419 induces STAT5 phosphorylation with high selectivity for CD8 and NK cells but not Treg. Concordantly, it stimulates the proliferation of purified human CD8 T cells and NK cells but not CTLL-2 cells. A single injection of ANV419 in mice results in strong induction of the proliferation marker Ki67 specifically in CD8 T cells and NK cells but not Tregs and a selective increase of the respective cell numbers in the spleen and peripheral blood of animals. Single agent anti-tumor activity was observed in checkpoint sensitive (H22) and resistant (Renca, B16F10) syngeneic mouse tumor models. Combination of ANV419 with trastuzumab in the gastric cancer N87 xenograft model in BALB/c nude mice led to significant tumor reduction relative to trastuzumab monotherapy. In non-human primates, ANV419 is well tolerated and induces expression of Ki67 and sustained expansion in CD8 T cells and NK cells with no signs of vascular leak syndrome observed with high dose aldesleukin in patients.ConclusionsThe pre-clinical data suggest that ANV419 possesses a unique structure and is potent in expanding CD8 T-cells and NK cells with a marked safety window in non-human primates. This data warrants further translational development of ANV419 as an immune therapeutic in oncology.

B-cell and T-cell values in peripheral blood in Polish mixed-breed rabbits with addition of blood of meet breeds

2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Laboratory Animals ◽  
Immunological Parameters ◽  
Four Seasons ◽  
Mixed Breed ◽  
The Impact

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.

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