scholarly journals Human Placental Cytotrophoblasts Attract Monocytes and Cd56bright Natural Killer Cells via the Actions of Monocyte Inflammatory Protein 1α

2001 ◽  
Vol 193 (10) ◽  
pp. 1199-1212 ◽  
Author(s):  
Penelope M. Drake ◽  
Michael D. Gunn ◽  
Israel F. Charo ◽  
Chia-Lin Tsou ◽  
Yan Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Conditioned Medium ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Chorionic Villus ◽  
Enzyme Linked Immunosorbent Assay ◽  
General Hypothesis ◽  
Inflammatory Protein

During human pregnancy, the specialized epithelial cells of the placenta (cytotrophoblasts) come into direct contact with immune cells in several locations. In the fetal compartment of the placenta, cytotrophoblast stem cells lie adjacent to macrophages (Hofbauer cells) that reside within the chorionic villus stroma. At sites of placental attachment to the mother, invasive cytotrophoblasts encounter specialized maternal natural killer (NK) cells (CD56bright), macrophages, and T cells that accumulate within the uterine wall during pregnancy. Here we tested the hypothesis that fetal cytotrophoblasts can direct the migration of these maternal immune cells. First, we assayed the chemotactic activity of cytotrophoblast conditioned medium samples, using human peripheral blood mononuclear cells as targets. The placental samples preferentially attracted NK cells (both CD56dim and CD56bright), monocytes, and T cells, suggesting that our hypothesis was correct. A screen to identify chemokine activity through the induction of a Ca2+ flux in cells transfected with individual chemokine receptors suggested that cytotrophoblasts secreted monocyte inflammatory protein (MIP)-1α. This was confirmed by localizing the corresponding mRNA and protein, both in vitro and in vivo. MIP-1α protein in conditioned medium was further characterized by immunoblotting and enzyme-linked immunosorbent assay. Immunodepletion of MIP-1α from cytotrophoblast conditioned medium showed that this chemokine was responsible for a significant portion of the induced monocyte and CD56bright NK cell chemotax-is. These data suggest the specific conclusion that cytotrophoblasts can attract monocytes and CD56bright NK cells by producing MIP-1α and the more general hypothesis that these cells may organize and act on leukocytes at the maternal–fetal interface.

scholarly journals Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hee Young Na ◽  
Yujun Park ◽  
Soo Kyung Nam ◽  
Jiwon Koh ◽  
Yoonjin Kwak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Nk Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Prognostic Significance

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.

scholarly journals Involvement of natural killer cells in the pathogenesis of endometriosis in patients with pelvic pain

2020 ◽  
Vol 48 (7) ◽  
pp. 030006051987140
Author(s):  
Jue He ◽  
Yan Xu ◽  
Minhui Yi ◽  
Cancan Gu ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Pelvic Pain ◽  
Immune Cells ◽  
Expression Profiles ◽  
Gradient Centrifugation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sterile Alpha Motif Domain ◽  
Factor Α ◽  
Protein Expression Profiles

Objectives To detect the involvement of immune cells in the pathogenesis of endometriosis in patients with stable status or pelvic pain. Methods Blood was collected from patients with endometriosis with and without pelvic pain. Natural killer (NK) and Th17 cells were analyzed by flow cytometry, and secretion of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-7) was verified by enzyme-linked immunosorbent assay. We isolated immune cells from blood by density-gradient centrifugation to investigate the expression of functional molecules including sterile alpha motif domain-containing protein 9 (SAMD9), Ral guanine nucleotide dissociation stimulator-like 2 (RGL2), early growth response protein 1, and Akirin2. We also searched the BIOGPS database for protein expression profiles. Results SAMD9 and RGL2 expression levels were significantly upregulated in patients with pelvic pain. Furthermore, lysophosphatidic acid receptor 1 expression was higher in endometrial tissues from patients with pelvic pain, and was mainly localized in stromal and glandular epithelial cells in ectopic lesions. Conclusion NK cells play an important role in the pathogenesis of endometriosis in patients with pelvic pain. Suppressing the cytotoxic activity of NK cells may thus help to reduce the progression of pelvic pain in patients with endometriosis.

scholarly journals INFLUENCE OF REGULATORY T CELLS ON THE FUNCTIONING OF NATURAL KILLER CELLS DURING CANCER IMMUNOTHERAPY

2012 ◽  
Vol 67 (4) ◽  
pp. 60-64
Author(s):  
I. O. Chikileva ◽  
I. Zh. Shubina ◽  
E. V. Kiselevskii
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Foxp3 Expression ◽  
Peripheral Blood Mononuclear ◽  
The Common

One of the common arguments against cancer immunotherapy based on natural killer (NK) cells activated in the presence of interleukin-2 (IL-2) is the probability of the activation of regulatory T cells (Tregs) by IL-2 besides NK cells. Thus, we have monitored numbers of FoxP3+CD4+CD25+ T cells in the samples of healthy volunteers’ peripheral blood mononuclear cells (PBMCs) cultured with or without IL-2. We observed marked increase in the percentages of the CD4+CD25+ T cells in the presence of IL-2. Proportions of Foxp3+CD4+CD25+ T cells feebly increased, remained on the same level or even decreased compared to PBMCs cultured without exogenous IL-2. Based on the absence of FoxP3 expression, most of the CD4+CD25+ T cells purified from IL-2 activated PBMCs were not Tregs, but activated Th cells. Moreover, the addition of the purified supposed Tregs to samples of activated NK cells never inhibited their cytotoxic reactions. 

scholarly journals A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erin H. Doyle ◽  
Costica Aloman ◽  
Ahmed El-Shamy ◽  
Francis Eng ◽  
Adeeb Rahman ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Function ◽  
Portal Vein ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Normal Liver ◽  
Multiparameter Flow Cytometry

AbstractViral hepatitis leads to immune-mediated liver injury. The rate of disease progression varies between individuals. We aimed to phenotype immune cells associated with preservation of normal liver function during hepatitis C virus (HCV) infection. Clinical data and specimens were obtained from 19 HCV-infected patients undergoing liver transplantation. Liver and peripheral blood mononuclear cells were isolated and eight subsets of innate immune cells were delineated by multiparameter flow cytometry. Cytokine assays and microarrays were performed. Intrahepatic CD56Bright/CD16- natural killer (NK) cells comprised the only subset correlating with better liver function, i.e., lower bilirubin (p = 0.0002) and lower model for end stage of liver disease scores (p = 0.03). The signature of liver NK cells from HCV-infected patients included genes expressed by NK cells in normal liver and by decidual NK cells. Portal vein blood had a higher concentration of interleukin (IL)-10 than peripheral blood (p = 0.03). LMCs were less responsive to toll-like receptor (TLR) stimulation than PBMCs, with fewer pro-inflammatory gene-expression pathways up-regulated after in vitro exposure to lipopolysaccharide and a TLR-7/8 agonist. Hepatic CD56Bright/CD16- NK cells may be critical for maintaining liver homeostasis. Portal vein IL-10 may prime inhibitory pathways, attenuating TLR signaling and reducing responsiveness to pro-inflammatory stimuli.

scholarly journals The immune cell landscape of peripheral blood mononuclear cells from PNS patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qing Ye ◽  
Chao Zhou ◽  
Sisi Li ◽  
Jingjing Wang ◽  
Fei Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Nephrotic Syndrome ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Immunological Mechanism

AbstractExisting research suggests that the human immune system and immune cells are involved in the pathogenesis of nephrotic syndrome, but there is still a lack of direct evidence. This study tried to analyze the profiling of immune cells in the peripheral blood of steroid-sensitive nephrotic syndrome (SSNS) patients and steroid-resistant nephrotic syndrome (SRNS) patients before and after standard steroid treatment to clarify the immunological mechanism of nephrotic syndrome patients. The number and proportion of CD4 + T cells in patients with nephrotic syndrome remained unchanged. However, there is an imbalance of Th1 and Th2 and an excessive increase of Th17 cells. The number of CD8 + T cells and the number of effector CD8 + T cells in them increased significantly, but only in SSNS, the number of activated CD8 + T cells increased, and the number of activated Treg cells decreased significantly. Nephrotic syndrome patients also have B cell disorder, and it is more prominent in SSNS patients. Compared with the normal control, only the number of B cells and plasmablast in SSNS patients increased significantly (Z = − 2.20, P = 0.028). This study also observed that transitional B cells decreased in both SSNS and SRNS patients, but SSNS patients' decrease was lower than in SRNS patients. Compared with normal controls, monocytes in patients with nephrotic syndrome decreased significantly. The main reason was that Non-classical Monocyte decreased, while Classical Monocyte increased slightly. The total number of NK cells did not change, but the internal cell subgroups' composition occurred. Changes, realized as CD56hi NK cells increased, CD56low NK cells decreased; and the above trend is more evident in SSNS patients. Patients with nephrotic syndrome have immune disorders, including T cells, B cells, Monocytes, and NK cells. It can be confirmed that immune factors are involved in the pathogenesis of the nephrotic syndrome.

Epinephrine-Induced Mobilization of Natural Killer (NK) Cells and NK-like T Cells in HIV-Infected Patients

1999 ◽  
Vol 197 (2) ◽  
pp. 91-98 ◽  
Author(s):  
Sisse R. Søndergaard ◽  
Henrik Ullum ◽  
Peter Skinhøj ◽  
Bente K. Pedersen
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer

scholarly journals γδ T Cells and NK Cells – Distinct Pathogenic Roles as Innate-Like Immune Cells in CNS Autoimmunity

2015 ◽  
Vol 6 ◽  
Author(s):  
Sarah C. Edwards ◽  
Aoife M. McGinley ◽  
Niamh C. McGuinness ◽  
Kingston H. G. Mills
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Γδ T Cells ◽  
Cns Autoimmunity

Engineered immunostimulatory cells can convert PBMCs from chronic lymphocytic leukemia (CLL) patients into potent tumor killing immune cells.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7517-7517
Author(s):  
Joshua W. Keegan ◽  
Frank Borriello ◽  
Stacey M. Fernandes ◽  
Jennifer R. Brown ◽  
James A. Lederer
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Killing Activity ◽  
Tumor Killing ◽  
Tumor Cell Killing ◽  
Potent Tumor

7517 Background: Alloplex Biotherapeutics has developed a cellular therapeutic that uses ENgineered Leukocyte ImmunoSTimulatory cell lines called ENLIST cells to activate and expand populations of tumor killing effector cells from human peripheral blood mononuclear cells (PBMCs). This process leads to a 300-fold expansion of NK cells, CD8+ T cells, NKT cells, and TCRγδ T cells that are called SUPLEXA cells, which will be cryopreserved and transferred back into patients as an autologous immune cell therapy for cancer. In this study, PBMCs from CLL patients were used to generate SUPLEXA cells as a first approach to comparatively profile SUPLEXA cells from cancer patients and normal healthy volunteers (NHVs). Methods: ENLIST cell lines were engineered by expressing curated immunomodulatory proteins in the SK-MEL-2 melanoma cell line. Two million (M) PBMCs from 10 CLL patients or 2 NHVs were incubated with 0.4 M freeze/thaw killed ENLIST cells for 5 days in XVIVO-15 medium with 2% heat-inactivated human AB serum (XAB2) and then split 1:15 in XAB2 containing IL-7 and IL-15 to expand. After 9 days, SUPLEXA cells were harvested and cryopreserved. Results: Original PBMCs and matched SUPLEXA cells from each donor were thawed and characterized by mass cytometry (CyTOF) using a 47-marker antibody panel. CyTOF staining results of PBMCs from CLL patients demonstrated approximately 95% leukemia cells and few T cells, NK cells, B cells, and monocytes. CyTOF staining of SUPLEXA cells from all 10 CLL patients showed expansion of NK cells (17%), CD8 T cells (11%), and CD4 T cells (7.5%) that were similar in phenotype to SUPLEXA cells from NHVs showing high expression of granzymes and perforin that are indicative of potent tumor cell killing activity. Cancer cells in the original CLL PBMC samples were reduced to 0.78%. However, a population of non-T/non-B cells (60% ± 9.5%) was detected in SUPLEXA cells from all CLL patients that require further characterization. Next, SUPLEXA cells from CLL and NHV patients were comparatively tested for tumor cell killing activity at 2:1, 1:1, and 1:2 effector to target cell (MEL-14 melanoma cells expressing RFP) ratios. Percent killing of tumor cells by SUPLEXA cells prepared from CLL patients (77.8% ± 2.6% at 2:1) and NHVs (81.5% ± 0.3% at 2:1) were nearly identical at all effector to target ratios. Conclusions: We demonstrate for the first time that PBMCs from CLL patients can be converted into SUPLEXA cells despite low numbers of normal immune cells at baseline and the known immunologic impairment present in CLL patients. Importantly, SUPLEXA cells derived from CLL patients acquire potent tumor killing activity that is indistinguishable from SUPLEXA cells prepared from NHVs. Taken together, these findings support the feasibility of converting PBMCs from CLL patients with low percentages of NK and T cells into an autologous cellular therapy for cancer.

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