scholarly journals Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanhong Li ◽  
Jiajia Chen ◽  
Yikong Lin ◽  
Ling Xu ◽  
Yifei Sang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Spontaneous Abortion ◽  
Immune Status ◽  
Normal Pregnancy ◽  
Reproductive Age ◽  
Chow Diet ◽  
Increased Risk ◽  
Maternal Immune Response

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

Specific features of T- and NK-cellular immunity in chronic lymphocytic leukemia

2021 ◽  
Vol 66 (6) ◽  
pp. 345-352
Author(s):  
Evgeniy Vladimirovich Pochtar ◽  
S. A. Lugovskaya ◽  
E. V. Naumova ◽  
E. A. Dmitrieva ◽  
A. I. Kostin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Lymphocytic Leukemia ◽  
Positive Trend ◽  
Functional Changes ◽  
Activated T Lymphocytes ◽  
T Helpers

Profound immunological dysfunction is the key factor determining the development of infectious complications in chronic lymphocytic leukemia (CLL). The aim of this work is to assess the features of the subpopulation composition of T-lymphocytes (T-helpers (Th), cytotoxic T-lymphocytes (Tcyt), T regulatory cells (Treg), T-NK cells, naive Th, Th-memory, activated T-lymphocytes, TCRγδ cells) and NK cells in peripheral blood of patients with newly diagnosed chronic lymphocytic leukemia (CLL) and receiving ibrutinib therapy. Hematological and immunophenotypic studies have been performed in 30 patients with previously untreated CLL, 122 patients on ibrutinib therapy and 20 healthy donors. The subpopulation composition of T-lymphocytes (Th, Tcyt, Treg, T-NK, naive T-helpers, memory T-helpers, TCRγδ cells, activated T-lymphocytes) and NK cells has been assessed on flow cytometer (FACSCanto II (BD)) using the following panel of monoclonal antibodies: CD45, CD19, CD3, CD4, CD5, CD8, TCRγδ, CD127, CD16, CD56, CD57 CD45RA, CD45R0, HLA-DR, CD25. Compared to controls all CLL samples were found to have higher the absolute number of T-lymphocytes, NK cells and their subpopulations, T-helpers (especially of memory T-cells), cytotoxic T-cells, regulatory T-cells, TCRγδ T-cells, activated T-lymphocytes, increased cytotoxic potential of NK cells in previously untreated CLL patients. Patients who received ibrutinib therapy have registered a positive trend towards recovery of the subpopulation composition of T-lymphocytes and NK-cells. CLL patients have been found to have quantitative and functional changes in the subpopulations of T-lymphocytes and NK cells, indicating dysregulation of the immune response, and a high risk of developing infections. Monitoring of immunological parameters for ibrutinib therapy make possible to estimate impact of ibrutinib on the adaptive anti-CLL immune response.

Abstract P097: Maternal Vascular Changes during Pregnancy may Persist Postpartum

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Nancy A Niemczyk ◽  
Emma Barinas-Mitchell ◽  
Janet M Catov ◽  
Candace K McClure ◽  
James M Roberts ◽  
...  
Keyword(s):  
Brachial Artery ◽  
Intima Media Thickness ◽  
Normal Pregnancy ◽  
Reproductive Age ◽  
Wave Form ◽  
Vascular Changes ◽  
Cvd Risk ◽  
Vascular Effects ◽  
Increased Risk ◽  
Artery Stiffness

Introduction: Higher parity (number of births) is associated with increased subclinical cardiovascular disease (CVD) in mid-life and older women, and with increased risk of CVD overall. In the only study of reproductive age women, common carotid artery intima-media thickness (CCA IMT) was greater after each birth. Prospective studies of arterial change throughout normal pregnancy are lacking; without them it is unclear whether unhealthy changes of the vasculature during pregnancy persist postpartum and raise women’s risk of CVD. The goal of this study was to prospectively assess normal vascular adaptation in healthy pregnant women. Hypotheses: During the course of healthy pregnancy: 1. CCA adventitial diameter (AD) will increase, then return to baseline postpartum, 2. CCA IMT will initially thin, then thicken as pregnancy progresses, then return to baseline postpartum, and 3. brachial artery distensibility will not change. Methods: We assessed 43 healthy women during each trimester of their first pregnancy and 6-8 weeks postpartum with B-mode ultrasound imaging of the CCA IMT and AD, independent predictors of CVD risk. Brachial artery distensibility, representing elasticity of the artery, was measured using the DynaPulse wave form analyzer. Linear mixed models were used to compare measures of CCA IMT, adventitial diameter, and brachial artery distensibility at each time point, after adjustment for age and pre-pregnancy BMI. Results: There were 37 women (age 28.2 ± 4.5 years, pre-pregnant BMI 24.4 ± 3.2 kg/m 2 ) with uncomplicated pregnancies. Six women with pregnancy complications were excluded from these analyses. After adjustment for age and pre-pregnancy BMI, mean (SE) CCA AD (mm) increased each trimester, from 6.38(0.08) in the 1 st trimester to 6.92(0.09) in the 3 rd trimester, and returned to baseline, 6.35 (0.07), postpartum. Pairwise comparisons were all statistically significant at p<.01. Mean (SE)CCA IMT (mm) was increased postpartum (0.567 (0.01)) compared to 1 st (0.539 (0.01)) and 2 nd trimester values (0.546 (0.01), p < .05 for each). Mean (SE) brachial artery distensibility (%/mmHg) decreased from 7.64 (0.28) 1st trimester to 6.84 (0.21) 3rd trimester (p < .01) and then remained unchanged at 6.82 (0.21) postpartum. Conclusions: As we hypothesized, in uncomplicated first pregnancies CCA AD increased throughout and returned to baseline postpartum. However, contrary to our hypotheses, CCA IMT increased postpartum, and the brachial artery stiffened during pregnancy and remained stiffer 6-8 weeks postpartum. In uncomplicated first pregnancies, some vascular changes resolved (CCA AD) and others persisted (CCA IMT and brachial artery stiffness). Whether this indicates that persistence of specific vascular effects of pregnancy may inform long term CVD risk remains to be explored.

scholarly journals Immunological effect of irreversible electroporation on solid tumors

2020 ◽  
Author(s):  
Xiaoxia Guo ◽  
Fang Du ◽  
Qin Liu ◽  
Yan Guo ◽  
Qingbing Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Irreversible Electroporation ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Activated T Cells ◽  
Immunological Effect ◽  
Immunological Effects ◽  
And Control

Abstract Background This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). Methods We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice. Results We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group. Conclusions Our study demonstrated that IRE not only induced immediate innate immune response dominated by the increase of neutrophils, monocytes and NK cells, but also upregulated activated T cells and downregulated Treg. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by cytotoxic CD8+ T cells.

scholarly journals Insulin Signaling in Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Cesare Tripolino ◽  
Jacopo Ciaffi ◽  
Valentina Pucino ◽  
Piero Ruscitti ◽  
Nina van Leeuwen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Insulin Signaling ◽  
Inflammatory Diseases ◽  
Cellular Membrane ◽  
Effect Relationship ◽  
Increased Risk ◽  
Environmental Agents ◽  
And Migration ◽  
Effect Of Glucose

Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.

scholarly journals Fertility preservation with successful pregnancy outcome in a patient with transplanted heart and non-Hodgkin’s lymphoma – a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ana Sofia Pais ◽  
Nuno Guerra ◽  
Daniela Couto ◽  
Ana Paula Sousa ◽  
Teresa Almeida-Santos
Keyword(s):  
Fertility Preservation ◽  
Heart Transplant ◽  
Multidisciplinary Team ◽  
Normal Pregnancy ◽  
Reproductive Age ◽  
Pelvic Irradiation ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Oncologic Treatment

Abstract Background: Fertility preservation must be discussed with reproductive age women before cancer treatment. Heart transplantation raises complex issues in pregnancy. Pregnancy in a heart transplant woman after pelvic irradiation involves close multidisciplinary follow-up to avoid complications in the mother and the foetus. We report the first live birth in a heart transplant woman after pelvic irradiation, chemotherapy and fertility preservation. Case presentation: A 36-year-old heart transplant woman with pelvic non-Hodgkin lymphoma spared her fertility, with cryopreservation of oocytes and embryos, before chemotherapy and pelvic irradiation. After multidisciplinary discussion and pre-conception evaluation, pregnancy was achieved. A close follow-up by a multidisciplinary team allowed a normal pregnancy without maternal or foetal complications and the delivery of a healthy infant. Conclusions Achieving pregnancy in heart transplant women with iatrogenic ovarian failure after oncologic treatment including pelvic irradiation is possible and can be successful. Careful and close surveillance by a multidisciplinary team is mandatory due to increased risk of maternal and foetal complications.

Elevated CD54 Expression Renders CD4+ T Cells Susceptible to Natural Killer Cell-Mediated Killing

2019 ◽  
Vol 220 (12) ◽  
pp. 1892-1903 ◽  
Author(s):  
Xi Chen ◽  
Huihui Chen ◽  
Zining Zhang ◽  
Yajing Fu ◽  
Xiaoxu Han ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd4 T Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune Response ◽  
Phenotypic Analysis

Abstract Background Natural killer (NK) cells are an important type of effector cell in the innate immune response, and also have a role in regulation of the adaptive immune response. Several studies have indicated that NK cells may influence CD4+ T cells during HIV infection. Methods In total, 51 HIV-infected individuals and 15 healthy controls participated in this study. We performed the flow cytometry assays and real-time PCR for the phenotypic analysis and the functional assays of NK cell-mediated deletion of CD4+ T cells, phosphorylation of nuclear factor-κB (NF-κB/p65) and the intervention of metformin. Results Here we detected high CD54 expression on CD4+ T cells in HIV-infected individuals, and demonstrate that upregulated CD54 is associated with disease progression in individuals infected with HIV. We also show that CD54 expression leads to the deletion of CD4+ T cells by NK cells in vitro, and that this is modulated by NF-κB/p65 signaling. Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-κB/p65 phosphorylation. Conclusions Our data suggest that further studies to evaluate the potential role of metformin as adjunctive therapy to reconstitute immune function in HIV-infected individuals are warranted.

scholarly journals Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

2008 ◽  
Vol 82 (21) ◽  
pp. 10820-10831 ◽  
Author(s):  
Subhadra Nandakumar ◽  
Stacie N. Woolard ◽  
Dorothy Yuan ◽  
Barry T. Rouse ◽  
Uday Kumaraguru
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Simplex Virus

ABSTRACT Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8+ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8+ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

scholarly journals The influence of the maternal uterine immune response on placentation in human subjects

1999 ◽  
Vol 58 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Ashley King ◽  
Y. W. Loke
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Intrauterine Growth Retardation ◽  
Human Subjects ◽  
Recognition System ◽  
Immunological Mechanism ◽  
Intrauterine Growth ◽  
Immunological Relationship ◽  
Maternal Immune Response ◽  
Clinical Problems

The immunological relationship beween the mammalian fetus and its mother during pregnancy has been considered similar to that between a transplanted allograft and its recipient ever since Medawar (1953) first proposed the concept of the ‘fetus as an allograft’ in the early 1950s. Based on this analogy, it has been assumed that implantation of the fetal placenta in the uterus would be controlled similarly by a maternal immune response mediated by T-cells recognizing paternally-derived alloantigens expressed by the placenta. Surprisingly, recent evidence suggests that implantation might involve predominantly a novel allogeneic recognition system based on natural killer cells rather than T-cells (Loke & King, 1995). The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is now the focus of intense research interest. Since aberrant implantation can cause a variety of clinical problems, including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimens to improve fetal growth and development.

scholarly journals DISCORDANT RESPONSE OF CD4+ T LYMPHOCYTES TO ANTIRETROVIRAL THERAPY

2019 ◽  
Vol 11 (1) ◽  
pp. 16-30 ◽  
Author(s):  
K. V. Shmagel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Viral Load ◽  
Immune System ◽  
Antiretroviral Therapy ◽  
T Lymphocytes ◽  
Lymphocyte Proliferation ◽  
Immune Reconstitution ◽  
Cell Counts ◽  
Increased Risk

Antiretroviral therapy (ART) in HIV infected patients generally results in the suppression of viral replication and reconstitution of CD4+ T lymphocytes cell counts. In some patients (about 20%), however, a disturbance in regeneration of immune competent cells with a background of low viral load occurs. The term «immunological nonresponders» has been used to describe this phenomenon. Discordant immune response to antiviral therapy may be caused by increasing of depletion and reducing of production of CD4+ T cells. However, mechanisms for low immune reconstitution are not currently well understood. «Immunological nonresponders» exhibit booster lymphocyte proliferation, increased immune activation and reducing of CD4+ T lymphocytes survival time in comparison with patients with concordant response to the therapy. Their immune system is characterized by more pronounced aging and exhaustion. This leads to early and frequent manifestation of AIDSrelated diseases. Besides, immunological nonresponders have an increased risk of non-AIDS-related diseases due to pronounced systemic inflammation. The objective of the present review was to highlight the important problem that is rather common on аntiretroviral therapy and to enlist the specialists to the solving of this issue.

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