The Role of Soluble Molecules CD25, CD38, and CD95 in the Development of Immunosuppression in Cytomegalovirus Infection

2021 ◽  
pp. 74-78
Author(s):  
VV Novikov ◽  
GA Kravchenko ◽  
DM Sobchak ◽  
DV Novikov ◽  
SV Shumilova
Keyword(s):  
Human Peripheral Blood ◽  
Polyclonal Antibodies ◽  
Laboratory Data ◽  
Cmv Infection ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pronounced Increase ◽  
Oligomeric Form ◽  
Cmv Disease

Introduction: Cytomegalovirus (CMV) infection is a common beta-herpesvirus infection widely spread in the human population. The proportion of infected population increases with age and approaches 100 % in elderly people. The infection is usually latent but is capable of reactivation when immunosuppression develops. The mechanisms of reactivation are not fully understood. The objective of our study was to evaluate the role of soluble molecules CD25, CD38, CD95 in the development of immunosuppression in CMV infection. Materials and methods: We used 18 serum samples from cases of CMV disease in the stage of reactivation, all confirmed by clinical and laboratory data. The patients received treatment in Nizhny Novgorod Infectious Disease Hospital No. 2. The serum content of the total and oligomeric soluble molecules CD25, CD38, and CD95 was identified by ELISA using monoclonal and polyclonal antibodies against human peripheral blood mononuclear cell proteins. The results were recorded spectrophotometrically and evaluated by converting optical density units to conventional units (U/mL). Results: We established an increase in the serum content of total and oligomeric fractions of soluble molecules CD25, CD38, and CD95 in the cases of CMV disease. While the serum content of the total and oligomeric fractions of molecules CD25 and CD38 increased equally, the oligomeric fraction of molecules СD95 demonstrated a more pronounced increase compared to the total fraction of these molecules. Our findings suggest the immune response suppression mechanism associated with initiation of apoptosis of effector T lymphocytes involving oligomeric form of molecules CD95. Conclusion: Changes in the content, structural and functional state of soluble differentiating molecules CD25, CD38, and CD95 indicate their involvement in immunosuppression mechanisms in patients with CMV infection.

Autocrine regulation of interleukin-8 production in human monocytes

2000 ◽  
Vol 279 (6) ◽  
pp. L1129-L1136 ◽  
Author(s):  
Darren D. Browning ◽  
Wade C. Diehl ◽  
Matthew H. Hsu ◽  
Ingrid U. Schraufstatter ◽  
Richard D. Ye
Keyword(s):  
Mononuclear Cells ◽  
De Novo ◽  
Human Peripheral Blood ◽  
Surface Expression ◽  
Polymorphonuclear Neutrophils ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Expression ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Activated Protein

Interleukin (IL)-8 is a C-X-C chemokine that plays an important role in acute inflammation through its G protein-coupled receptors CXCR1 and CXCR2. In this study, we investigated the role of IL-8 as an autocrine regulator of IL-8 production and the signaling mechanisms involved in human peripheral blood mononuclear cells (MNCs). Sepharose-immobilized IL-8 stimulated a sevenfold increase in IL-8 production within 2 h. IL-8 induced the expression of its own message, and IL-8 biosynthesis was inhibited by cycloheximide and actinomycin D, indicating de novo RNA and protein synthesis. In contrast to MNCs, polymorphonuclear neutrophils did not respond to the immobilized IL-8 with IL-8 production despite cell surface expression of CXCR1 and CXCR2. Melanoma growth-stimulatory activity/growth-related protein-α (MGSA/GROα), which binds CXCR2 but not CXCR1, was unable to either stimulate IL-8 secretion in MNCs or desensitize these cells to respond to immobilized IL-8. The involvement of mitogen-activated protein kinase (MAPK) in IL-8-induced IL-8 biosynthesis was suggested by the ability of PD-98059, an inhibitor of MAPK kinase, to block this function. Furthermore, IL-8 induced a significant increase in extracellular signal-regulated kinase 2 phosphorylation, whereas MGSA/GROα was much less effective. These findings support the role of IL-8 as an autocrine regulator of IL-8 production and suggest that this function is mediated by CXCR1 through activation of MAPK.

scholarly journals Control of hsp70 RNA levels in human lymphocytes.

1987 ◽  
Vol 104 (2) ◽  
pp. 183-187 ◽  
Author(s):  
L Kaczmarek ◽  
B Calabretta ◽  
H T Kao ◽  
N Heintz ◽  
J Nevins ◽  
...  
Keyword(s):  
Culture Medium ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Human Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Growth State ◽  
Steady State Levels ◽  
Rna Blots

The expression of a hsp70 gene in human cells has previously been shown to be related to the growth state of the cells. As an alternative to in vitro synchronization procedures, we have measured steady-state levels of the RNA for a heat-shock protein 70 (hsp70) in human peripheral blood mononuclear cells (PBMC) that are naturally quiescent in a G0 state. The probe used recognized, on RNA blots, one single band. The levels of this hsp70 RNA are elevated in circulating PBMC and decrease when the cells are incubated with serum, or phytohemagglutinin, or simply when they are incubated in culture medium. The levels of hsp70 RNA decrease within 30 min after in vitro culture, and are accompanied by an increase in the levels of c-fos RNA. These findings, together with other recent reports in the literature, suggest a possible role of the hsp70 proteins in the regulation of cell growth.

High levels of thyroid hormone impair regulatory T cells function via reduced PD-1 expression

2021 ◽  
Author(s):  
Yi Zhong ◽  
Ting-Ting Lu ◽  
Xiao-Mei Liu ◽  
Bing-Li Liu ◽  
Yun Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Hormone ◽  
Regulatory T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

Abstract Context Regulatory T cells (Tregs) dysfunction plays an important role in the development and progression of Graves’ disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Tregs expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. Objective To evaluate the role of PD-1 in Tregs function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. Methods We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Tregs function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. Results PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Tregs function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. Conclusions Tregs dysfunction in GD patients might be due to down-regulation of PD-1 expression in Tregs induced by high levels of serum T3.

scholarly journals TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins

2019 ◽  
Vol 116 (12) ◽  
pp. 5705-5714 ◽  
Author(s):  
Minghua Li ◽  
Abdul A. Waheed ◽  
Jingyou Yu ◽  
Cong Zeng ◽  
Hui-Yu Chen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Ectopic Expression ◽  
Metabolic Labeling ◽  
Peripheral Blood Mononuclear ◽  
Enveloped Viruses ◽  
Intracellular Compartments ◽  
Hiv 1

The T cell Ig and mucin domain (TIM) proteins inhibit release of HIV-1 and other enveloped viruses by interacting with cell- and virion-associated phosphatidylserine (PS). Here, we show that the Nef proteins of HIV-1 and other lentiviruses antagonize TIM-mediated restriction. TIM-1 more potently inhibits the release of Nef-deficient relative to Nef-expressing HIV-1, and ectopic expression of Nef relieves restriction. HIV-1 Nef does not down-regulate the overall level of TIM-1 expression, but promotes its internalization from the plasma membrane and sequesters its expression in intracellular compartments. Notably, Nef mutants defective in modulating membrane protein endocytic trafficking are incapable of antagonizing TIM-mediated inhibition of HIV-1 release. Intriguingly, depletion of SERINC3 or SERINC5 proteins in human peripheral blood mononuclear cells (PBMCs) attenuates TIM-1 restriction of HIV-1 release, in particular that of Nef-deficient viruses. In contrast, coexpression of SERINC3 or SERINC5 increases the expression of TIM-1 on the plasma membrane and potentiates TIM-mediated inhibition of HIV-1 production. Pulse-chase metabolic labeling reveals that the half-life of TIM-1 is extended by SERINC5 from <2 to ∼6 hours, suggesting that SERINC5 stabilizes the expression of TIM-1. Consistent with a role for SERINC protein in potentiating TIM-1 restriction, we find that MLV glycoGag and EIAV S2 proteins, which, like Nef, antagonize SERINC-mediated diminishment of HIV-1 infectivity, also effectively counteract TIM-mediated inhibition of HIV-1 release. Collectively, our work reveals a role of Nef in antagonizing TIM-1 and highlights the complex interplay between Nef and HIV-1 restriction by TIMs and SERINCs.

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