Adaptive Cellular Responses following SARS-CoV-2 Vaccination in Primary Antibody Deficiency Patients.

Since the start of the COVID-19 pandemic, in a short span of 3 years, vaccination against SARS-CoV-2 has resulted in the end of the pandemic. Patients with inborn errors of immunity (IEI) are at an increased risk for SARS-CoV-2 infection; however, serious illnesses and mortality, especially in primary antibody deficiencies (PADs), have been lower than expected and lower than other high-risk groups. This suggests that PAD patients may mount a reasonable effective response to the SARS-CoV-2 vaccine.

Molecular changes associated with increased TNF-α-induced apoptotis in naïve (T) and central memory (T) CD8+ T cells in aged humans.

Background: Progressive T cell decline in aged humans is associated with a deficiency of naïve (T) and central memory (T) T cells. We have previously reported increased Tumor necrosis factor-α (TNF-α)-induced apoptosis in T and T T cells in aged humans; however, the molecular basis of increased apoptosis remains to be defined. Since expression of TNF receptors (TNFRs) was reported to be comparable in young and aged, we investigated signaling events downstream of TNFRs to understand the molecular basis of increased TNF-α-induced apoptosis in aged T and T CD8+ cells.

FcμR in human B cell subsets in primary selective IgM deficiency, and regulation of FcμR and production of natural IgM antibodies by IGIV.

IgMFcR (FcμR) are expressed on B cell and B cell subsets. Mice deficient in secreted IgM and FcμR share properties of impaired specific antibody response and autoimmunity with patient with selective IgM deficiency (SIGMD). Intravenous immunoglobulin (IGIV) regulates immune response, including modulation of IgGFc receptors.

Reversal of oxidative stress-induced apoptosis in T and B lymphocytes by Coenzyme Q10 (CoQ10).

Coenzyme Q10, (CoQ10) an electron transporter and an antioxidant, protects a variety of cell types against oxidative stress and apoptosis. However, protective effect of CoQ10 on oxidative stress-induced apoptosis in lymphocytes has not been studied in detail. In this study, we investigated the effect of CoQ10 on oxidative stress-induced apoptosis in lymphocytes.

Dendritic cells from the elderly display an intrinsic defect in the production of IL-10 in response to lithium chloride.

Chronic, low grade inflammation is a characteristic of old age. Innate immune system cells such as dendritic cells (DCs) from the elderly display a pro-inflammatory phenotype associated with increased reactivity to self. Lithium is a well-established anti-inflammatory agent used in the treatment of bipolar disorders.

Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans.

Aging is associated chronic inflammation and autoimmunity, and increased levels of leptin. Increased levels of leptin are associated with inflammation and autoimmunity. We have recently reported that leptin activates B cells to induce secretion of proinflammatory and anti-inflammatory cytokines.

Iron sucrose impairs phagocytic function and promotes apoptosis in polymorphonuclear leukocytes.

Background: With the recent implementation of bundling reimbursement policy, the use of intravenous (IV) iron preparations for the management of anemia in the end-stage renal disease (ESRD) population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of polymorphonuclear leukocytes (PMNs) against Escherichia coli.

Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway.

Leptin, one of the adipokines, functions as a hormone and a cytokine. In this investigation, we show for the first time that leptin, in a concentration-dependent manner, activates human peripheral blood B cells to induce secretion of IL-6, IL-10, and TNF-α. Leptin increased B cells expressing CD25 and HLA-DR.

Impaired functions of peripheral blood monocyte subpopulations in aged humans.

Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14(++(high))CD16(-), CD14(+(low))CD16(-), CD14(++(high))CD16(+), and CD14(+(low))CD16(+)) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14(++(high))CD16(+) and CD14(+(low))CD16(+) monocytes were significantly increased, whereas proportions of CD14(+(low))CD16(-) monocytes were decreased in aged subjects as compared to young subjects.

Impaired pneumovax-23-induced monocyte-derived cytokine production in patients with common variable immunodeficiency.

Introduction: Streptococcus pneumoniae is one of the most common infectious pathogens in common variable immunodeficiency (CVID). Both innate and adaptive immune response appears to play a role in defense against S. pneumoniae.

Age-related alterations of gene expression patterns in human CD8+ T cells.

Aging is associated with progressive T-cell deficiency and increased incidence of infections, cancer and autoimmunity. In this comprehensive study, we have compared the gene expression profiles in CD8+ T cells from aged and young healthy subjects using Affymetrix microarray Human Genome U133A-2 GeneChips. A total of 5.

Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression.

Background: End-stage renal disease (ESRD) results in increased susceptibility to infections, impaired response to vaccination and diffuse B-cell lymphopenia. However, the precise nature and mechanism of ESRD-induced B-cell lymphopenia remains unclear. Therefore, we studied the distribution of major B-cell subsets, B-cell growth, differentiation and survival factors, IL-7 and BAFF, and their receptors in 21 haemodialysis patients and 21 controls.

Susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM) in vitro.

Prostate cancer is one of the most frequent cancers among men in the United States. In the current study, we examined the susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM), a crystallized mixture of minerals and trace elements from sea water, in vitro. Cancer cells were cultured with MCM at different concentrations (0-1000 microg/ml).

An iron-based beverage, HydroFerrate fluid (MRN-100), alleviates oxidative stress in murine lymphocytes in vitro.

Background: Several studies have examined the correlation between iron oxidation and H(2)O(2) degradation. The present study was carried out to examine the protective effects of MRN-100 against stress-induced apoptosis in murine splenic cells in vitro. MRN-100, or HydroFerrate fluid, is an iron-based beverage composed of bivalent and trivalent ferrates.

Differential effect of human herpesvirus 6A on cell division and apoptosis among naive and central and effector memory CD4+ and CD8+ T-cell subsets.

The immune responses of naive and different memory subsets of CD4(+) and CD8(+) T cells to human herpesvirus 6 (HHV-6) have not been previously investigated. We show that HHV-6A induces cell division, as measured by 5,6-carboxyfluorescein succinimidyl ester dye and flow cytometry, predominantly in two populations of effector memory CD4(+) and CD8(+) T cells (T(EM) and T(EMRA)); naïve (T(N)) and central memory (T(CM)) CD4(+) and CD8(+) T cells showed almost no cell division. In contrast, HHV-6A induced apoptosis primarily in T(N) and T(CM) CD4(+) and CD8(+) T cells, whereas T(EM) and T(EMRA) CD4(+) and CD8(+) T cells were resistant to HHV-6A-induced apoptosis.

S. cerevisiae induces apoptosis in human metastatic breast cancer cells by altering intracellular Ca2+ and the ratio of Bax and Bcl-2.

We have recently demonstrated that non-metastatic human breast cancer cell lines undergo apoptosis following phagocytosis of S. cerevisiae. In this study, we investigated the apoptotic effect of heat-killed yeast against human metastatic breast cancer (MBC) cells, MDA-MB-231 in vitro, and the underlying mechanistic bases of this effect.

Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in vitro through the mitochondrial pathway.

Previous studies have shown that thymic extracts possess antitumor and antimetastatic properties, but the mechanisms are not completely understood. Therefore, in this study the ability of the gross thymic extract Thymax to induce apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated. Tumor cells were cultured with different concentrations of Thymax for 24 h and the apoptotic response was assessed by propidium iodide and TUNEL assays.

MGN-3/Biobran, modified arabinoxylan from rice bran, sensitizes human breast cancer cells to chemotherapeutic agent, daunorubicin.

Background: MGN-3/Biobran, a modified form of arabinoxylan from rice bran, is a potent biological response modifier (BRM). Our previous studies demonstrated that MGN-3 sensitizes human leukemia cells to death receptor [CD95]-induced apoptosis [Ghoneum M, Gollapudi S. MGN-3 sensitizes human T cell leukemia cells to death receptor (CD95)-induced apoptosis.

Artemisia princeps var orientalis induces apoptosis in human breast cancer MCF-7 cells.

Background: Dried leaves of Artemisia princeps var orientalis are used in the Eastern practice of moxibustion to improve general health. The ability of A. princeps smoke and water extracts to induce apoptosis was evaluated in human breast cancer MCF-7 cells in vitro.

CD95-mediated apoptosis in naïve, central and effector memory subsets of CD4+ and CD8+ T cells in aged humans.

Aging is associated with a decrease in naïve (T(N)) and central memory (T(CM)), and an accumulation of effector memory (T(EM) and T(EMRA)) T cell subsets. Previously, we have demonstrated an increased sensitivity of T(N) and T(CM) CD4+ and CD8+ T cells in aging to TNF-alpha-induced apoptosis. In this investigation, we examined whether similar differential sensitivity is applicable to CD95-mediated apoptosis.

Effector memory CD8+ T cells are resistant to apoptosis.

Based upon their migrating properties and effector functions, CD8(+) T cells have been further classified into central memory (T(CM)) and two types of effector memory (T(EM) and T(EMRA)) cells. These memory cells display distinct replicative characteristics. Because apoptosis plays an important role in cellular homeostasis, we have examined the relative sensitivity of naïve (T(N)) and different memory CD8(+) T cells to apoptosis.

Susceptibility of naïve and subsets of memory T cells to apoptosis via multiple signaling pathways.

Apoptosis is mediated via death receptor, the mitochondrial, and the endoplasmic reticulum pathway. Following activation of naïve T cells with antigens, different subsets of memory T cells are generated. In this review we have discussed relative sensitivity/resistance of naïve and different subsets of memory T cells to apoptosis via different signaling pathways.

Yeast therapy for the treatment of breast cancer: a nude mice model study.

Background: Studies have demonstrated that phagocytosis of yeast induces apoptosis in human breast cancer (BC) cells in vitro. Here, the in vivo apoptotic activity of the S. cerevisiae against human BC (MCF-7) bearing nude mice was investigated.

Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating the expression of Bax and Bim in human B cells.

Arsenic trioxide (As2O3) has been approved for the treatment of acute promyelocytic leukemia (APML) and it is a promising candidate for the treatment of patients with lymphoproliferative disorders, such as relapsed or refractory multiple myeloma and myelodysplastic syndromes. The effects of As2O3 on B cells, specifically which do not express Bcl-2, have not been studied. In this study, we have demonstrated that As2O3, at clinically achievable therapeutic concentrations, induces apoptosis in Bcl-2 negative human B cell line Ramos.