scholarly journals Neutrophils and lymphopenia, an unknown axis in severe COVID-19 disease

2021 ◽  
Vol 17 (9) ◽  
pp. e1009850
Author(s):  
Hernán F. Peñaloza ◽  
Janet S. Lee ◽  
Prabir Ray
Keyword(s):  
T Lymphocytes ◽  
Neutralizing Antibodies ◽  
Distress Syndrome ◽  
Severe Disease ◽  
Physiological Role ◽  
Suppressor Cells ◽  
Current Evidence ◽  
Cell Responses ◽  
B And T Lymphocytes

The Coronavirus Disease 2019 (COVID-19) is caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus that can mediate asymptomatic or fatal infections characterized by pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Several studies have highlighted the importance of B and T lymphocytes, given that neutralizing antibodies and T cell responses are required for an effective immunity. In addition, other reports have described myeloid cells such as macrophages and monocytes play a major role in the immunity against SARS-CoV-2 as well as dysregulated pro-inflammatory signature that characterizes severe COVID-19. During COVID-19, neutrophils have been defined as a heterogeneous group of cells, functionally linked to severe inflammation and thrombosis triggered by degranulation and NETosis, but also to suppressive phenotypes. The physiological role of suppressive neutrophils during COVID-19 and their implications in severe disease have been poorly studied and is not well understood. Here, we discuss the current evidence regarding the role of neutrophils with suppressive properties such as granulocytic myeloid-derived suppressor cells (G-MDSCs) and their possible role in suppressing CD4+ and CD8+ T lymphocytes expansion and giving rise to lymphopenia in severe COVID-19 infection.

The role of STAT5 in the development, function, and transformation of B and T lymphocytes

2011 ◽  
Vol 1217 (1) ◽  
pp. 18-31 ◽  
Author(s):  
Lynn M. Heltemes-Harris ◽  
Mark J. L. Willette ◽  
Kieng B. Vang ◽  
Michael A. Farrar
Keyword(s):  
T Lymphocytes ◽  
B And T Lymphocytes

scholarly journals Preexisting Virus-Specific T Lymphocytes-Mediated Enhancement of Adenovirus Infections to Human Blood CD14+ Cells

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 154
Author(s):  
Fengling Feng ◽  
Jin Zhao ◽  
Pingchao Li ◽  
Ruiting Li ◽  
Ling Chen ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Viral Infection ◽  
Viral Infections ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Activation Markers ◽  
Gm Csf ◽  
Cell Responses ◽  
Underlying Mechanisms

Antigen-specific T lymphocytes play a critical role in controlling viral infections. However, we report here that preexisting virus-specific T cell responses also contribute to promoting adenovirus (Ad) infection. Previously, we found that CD14+ monocytes from Ad-seropositive individuals exhibited an increased susceptibility to Ad infection, when compared with that of Ad-seronegative individuals. But the underlying mechanisms for this enhancement of viral infection are not completely clarified. In this study, we found that the efficacy of Ad infection into CD14+ monocytes was significantly decreased after CD3+ T lymphocytes depletion from PBMC samples of Ad-seropositive individuals. In contrast, adding virus-specific CD3+ T lymphocytes into PBMC samples of Ad-seronegative individuals resulted in a significant increase of infection efficacy. CD3+ T lymphocytes in PBMC samples from Ad-seropositive individuals were more sensitive to be activated by adenovirus stimulus, characterized by upregulation of multiple cytokines and activation markers and also enhancement of cell proliferation. Further studies demonstrated that GM-CSF and IL-4 can promote Ad infection by up-regulating the expression of scavenger receptor 1 (SR-A) and integrins αVβ5 receptor of CD14+ cells. And taken together, these results suggest a novel role of virus-specific T cells in mediating enhancement of viral infection, and provide insights to understand the pathogenesis and complicated interactions between viruses and host immune cells.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

scholarly journals HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+T Cell Responses

2015 ◽  
Vol 90 (5) ◽  
pp. 2208-2220 ◽  
Author(s):  
Srinika Ranasinghe ◽  
Damien Z. Soghoian ◽  
Madelene Lindqvist ◽  
Musie Ghebremichael ◽  
Faith Donaghey ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Cell Responses

ABSTRACTAntigen-specific CD4+T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+T cells and, to a lesser extent, gp41-specific CD4+T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.IMPORTANCEOne of the earliest discoveries related to CD4+T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.

Immune mechanisms: adaptive immunity

2016 ◽  
Author(s):  
Maxime Breban ◽  
Hill Gaston
Keyword(s):  
T Cells ◽  
Animal Models ◽  
Inflammatory Response ◽  
Adaptive Immunity ◽  
Axial Spondyloarthritis ◽  
Human Peripheral Blood ◽  
Antibody Responses ◽  
Cell Responses ◽  
B And T Lymphocytes

The role of adaptive immunity (i.e. the involvement of B and T lymphocytes) in the pathogenesis of axial spondyloarthritis has been investigated in both human disease and relevant animal models. Studies of B cell responses have not generally implicated an autoantibody in the disease, but there are abnormalities of antibody responses, particularly increased titres of antibodies to various gut bacteria. T cells are critical to the disease in animal models other than those where overexpression of a cytokine is engineered, suggesting that they are the drivers of the inflammatory response. There is convergent evidence from animal models, genetics in humans, and direct observation of human peripheral blood and joints to implicate T cells producing IL-17 under the influence of IL-23. These in turn may be responding to bacteria either in the gut or on the skin.

Myeloid-Derived Suppressor Cells in Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2794-2794
Author(s):  
Els Van Valckenborgh ◽  
Jo Van Ginderachter ◽  
Kiavash Movahedi ◽  
Eline Menu ◽  
Karin Vanderkerken
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cell ◽  
Suppressor Cells ◽  
T Cell Responses ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
T Cell Suppression ◽  
Cell Suppression

Abstract Abstract 2794 Poster Board II-770 Myeloid-derived suppressor cells (MDSCs) are a heterogeneous mix of myeloid cells in different maturation stages generated in the bone marrow. The role of MDSCs in cancer is to suppress T-cell responses, thereby likely regulating tumor progression. In mice, MDSCs are identified by the expression of the surface markers CD11b and Gr-1. Recently, Ly6G+ granulocytic (PMN-MDSC) and Ly6G− monocytic (MO-MDSC) subsets could be distinguished (Movahedi et al. Blood 2008, 111:4233-44). In multiple myeloma patients, the immune function is impaired and this is caused by an immunologically hostile microenvironment and cellular defects, such as decreased numbers of immune cells, and DC or T-cell dysfunction. However, the role of MDSCs in immune suppression in multiple myeloma is not yet described. In this study, we investigated the immunosuppressive activity and mechanism of MDSC subsets in the syngeneic and immunocompetent 5TMM mouse model (5T2 and 5T33 models). In first instance, CD11b+Ly6G− and CD11b+Ly6G+ lineage-committed myeloid MDSC subsets were detected in 5TMM-diseased bone marrow by flow cytometry. These subsets were purified via MACS from the bone marrow of naïve and 5TMM tumor-bearing mice, and analyzed for T-cell suppressive activity. Hereto, CD8+ TCR-transgenic OT-1 splenocytes were stimulated with ovalbumin protein in the presence of purified MDSC subsets, after which T-cell proliferation was measured via 3H-thymidine incorporation. Both MDSC subsets from 5TMM bone marrow were able to suppress antigen-specific T-cell responses at a higher level compared to purified MDSC subsets from normal bone marrow. On average, Ly6G− MDSCs were more suppressive than Ly6G+ MDSCs. The 5T2MM model has a tumor take of approximately 12 weeks. Three weeks after intravenous inoculation of the tumor cells, the suppressive effect of the myeloid subsets was already observed (while the plasmacytosis in the BM was very low and no detectable serum M spike was observed), indicating that T-cell suppression is an early event in MM development. To unravel the suppressive mechanism of the MDSC subsets, inhibitors were used in ovalbumin-stimulated cocultures. Ly6G− MDSC-mediated suppression was partially reversed by the iNOS inhibitor L-NMMA and the COX-2 inhibitor sc-791, both of which lower the NO concentration in culture. In contrast, superoxide dismutase and especially catalase enhance NO concentrations, resulting in enhanced T-cell suppression. None of these inhibitors had any impact on the Ly6G+ MDSC-mediated suppression. In conclusion, these data reveal the presence of MDSCs as a novel immune suppressive strategy employed by multiple myeloma cells in the bone marrow, already occurring early in the disease process. Disclosures: No relevant conflicts of interest to declare.

Role of B and T lymphocytes in the specific immunosuppression induced by a protein released by a protein monocytes infected with African swine fever virus

1991 ◽  
Vol 3 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Adilia dos Santos Ribelro ◽  
Mário Passalaqua Arala-Chaves ◽  
Manuel Vilanova ◽  
Maria Teresa Porto ◽  
Antonio Coutinho
Keyword(s):  
T Lymphocytes ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
B And T Lymphocytes ◽  
Specific Immunosuppression

scholarly journals Evaluation of the association between exosomal levels and female reproductive system and fertility outcome during aging: a systematic review protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Halimeh Mobarak ◽  
Reza Rahbarghazi ◽  
Francesca Lolicato ◽  
Mohammad Heidarpour ◽  
Fariba Pashazadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reproductive System ◽  
Reproductive Tract ◽  
Physiological Role ◽  
Current Evidence ◽  
Gene Expressions ◽  
Younger Women ◽  
Age Related ◽  
Maternal Aging

Abstract Background Exosomes may have critical roles in the maternal-embryo cross-talk for the recognition and maintenance of pregnancy during maternal aging. Exosomes have the capability to carry developmental signaling molecules with the ability to modulate gene expressions and affect growth and regulation of embryo during pregnancy. Systematic review aims to evaluate age-related alterations in the exosomal content and functions that can influence the reproductive performance in human and animal models as conveyors of senescence signals. Methods A literature search of electronic databases including MEDLINE (PubMed), Embase, ProQuest, Scopus, Google Scholar, WHO, SID, MAGIRAN, and Barakat will be conducted. Following the online search, articles will be screened by two independent reviewers according to inclusion and exclusion criteria. Eligible studies will be critically appraised by reviewers at the study level for methodological quality using Joanna Briggs Institute’s standardized critical appraisal tools. The extracted data from selected studies will cover the study populations, methods, current evidence about the physiological role of extracellular vesicles and exosomes in reproductive system, relevant outcomes, and possible conclusions about the effectiveness of exposure. Discussion Regarding the role of exosomes and their cargoes in the function of reproductive tract, the possible beneficial or adverse effects following exosomal administration from younger women to older women will be evaluated in the systematic review. As a result, exosome therapy could be suggested as a novel therapeutic agent if the favorable results are identified.

scholarly journals Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VII. Idiotype-specific suppression of plaque-forming cell responses.

1981 ◽  
Vol 153 (3) ◽  
pp. 640-652 ◽  
Author(s):  
D H Sherr ◽  
S T Ju ◽  
J Z Weinberger ◽  
B Benacerraf ◽  
M E Dorf
Keyword(s):  
B Cells ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
In Vitro System ◽  
Specific Suppression ◽  
Cell Responses ◽  
T Suppressor Cells

The ability of suppressor cells induced by the intravenous administration of 4-hydro-3-nitrophenyl acetyl (NP)-modified syngeneic cells to reduce an idiotypic B cell response was studied in both an in vivo and an in vitro system. Idiotype-positive B cells were assayed by the ability of guinea pig anti-idiotypic antiserum to specifically inhibit idiotype-positive plaque formation. It was found that up to 57% of the PFC response in vivo and 100% of the PFC response in vitro was inhibitable with antiidiotypic antiserum. The expression of these idiotype-positive B cells could be suppressed by the transfer of spleen cells form mice treated 7 d previously with NP coupled syngeneic cels. T cells are both required and sufficient for the transfer of idiotype specific suppression. The induction of these idiotype-specific T suppressor cells directly with antigen suggests that recognition of unique determinants on cell surfaces is important for regulation of lymphoid cell interactions. The role of idiotype-specific suppressor cells in the network of lymphoid interactions is discussed.

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