scholarly journals Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bing Liu ◽  
Junyan Han ◽  
Xiaohuan Cheng ◽  
Long Yu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Healthy Subjects ◽  
Laboratory Data ◽  
Disease Onset ◽  
Lymphocyte Subpopulations ◽  
Laboratory Findings ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract COVID-19 has been widely spreading. We aimed to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n = 37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison (HC). Compared with PA patients, PP patients had much improved laboratory findings. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.

scholarly journals Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients

2020 ◽  
Author(s):  
Bing Liu ◽  
Junyan Han ◽  
Xiaohuan Cheng ◽  
Long Yu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Immune Cells ◽  
Healthy Subjects ◽  
Laboratory Data ◽  
Adaptive Immune System ◽  
Lymphocyte Subpopulations ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractBackgroundCOVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding.Methods37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison.ResultsCompared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative.ConclusionPersistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.SummaryDefects in adaptive immune system, including reduced T cells and B cells, were frequently observed in non-severe COVID-19 patients with persistent SARS-CoV-2 shedding. Assessment of immune system could be clinically relevant for discharge management.

scholarly journals The impact of body mass index on adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

Body mass index affects adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Body Mass ◽  
Immune Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. Recently, the importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown. Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV - and CMV + groups. Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8 + T cells was reduced. In addition, the frequency of B cells and CD4 + T cells positively correlated with BMI in the BM of CMV - persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons. Conclusion. Our work suggests that obesity may represent an independent risk factor supporting immunosenescence, in addition to aging and CMV. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

scholarly journals The Complexity of Microglial Interactions With Innate and Adaptive Immune Cells in Alzheimer’s Disease

2020 ◽  
Vol 12 ◽  
Author(s):  
Season K. Wyatt-Johnson ◽  
Randy R. Brutkiewicz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Reactive Microglia ◽  
Adaptive Immune Cells ◽  
Affected Relative ◽  
Peripheral Immune Cells

In the naïve mouse brain, microglia and astrocytes are the most abundant immune cells; however, there is a complexity of other immune cells present including monocytes, neutrophils, and lymphocytic cells, such as natural killer (NK) cells, T cells, and B cells. In Alzheimer’s disease (AD), there is high inflammation, reactive microglia, and astrocytes, leaky blood–brain barrier, the buildup of amyloid-beta (Aβ) plaques, and neurofibrillary tangles which attract infiltrating peripheral immune cells that are interacting with the resident microglia. Limited studies have analyzed how these infiltrating immune cells contribute to the neuropathology of AD and even fewer have analyzed their interactions with the resident microglia. Understanding the complexity and dynamics of how these immune cells interact in AD will be important for identifying new and novel therapeutic targets. Thus, this review will focus on discussing our current understanding of how macrophages, neutrophils, NK cells, T cells, and B cells, alongside astrocytes, are altered in AD and what this means for the disorder, as well as how these cells are affected relative to the resident microglia.

scholarly journals P01.10 IFNy secretion of adaptive and innate immune cells as a parameter to display leukaemia derived dendritic cell (DCleu) mediated immune responses in AML

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A13.1-A13
Author(s):  
LK Klauer ◽  
O Schutti ◽  
S Ugur ◽  
F Doraneh-Gard ◽  
N Rogers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Cells ◽  
Gm Csf ◽  
Adaptive Immune ◽  
Cik Cells ◽  
Adaptive Immune Cells ◽  
Suitable Parameter

BackgroundMyeloid leukaemic blasts can be converted into leukaemia derived dendritic cells (DCleu) with blastmodulatory Kit-I and Kit-M, which have the competence to regularly activate T and immunoreactive cells to gain anti-leukaemic activity or rather cytotoxicity. As innate and adaptive immune responses are notably promoted by the cytokine interferon gamma (IFNy), we hypothesised that the IFNy secretion could be a suitable parameter to display DC/DCleu mediated immunologic activity and even anti-leukaemic cytotoxicity.Materials and MethodsDC/DCleu were generated from leukaemic WB with Kit-I (GM-CSF + OK-432) and Kit-M (GM-CSF + PGE1) and used to stimulate T cell enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay (CTX). Initiated IFNy secretion of innate and adaptive immune cells (T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells, NKCD161+ cells, CIKCD56+ cells, CIKCD161+ cells and iNKT) was investigated with a cytokine secretion assay (CSA). In some cases IFNy production was additionally evaluated with an intracellular cytokine assay (ICA). Conclusively, the IFNy secretion of immunoreactive cells was correlated with the anti-leukaemic cytotoxicity.ResultsSignificant amounts of DC and DCleu as well as migratory DC and DCleu could be generated with Kit-I and Kit-M without induction of blast proliferation. T cell enriched immunoreactive cells stimulated with DC/DCleu showed an increased anti-leukaemic cytotoxicity and an increased IFNy secretion of T, NK and CIK cells compared to control. Both the CSA and ICA yielded comparable amounts of IFNy positive innate and adaptive immune cells. The correlation between the IFNy secretion of immunoreactive cells and the anti-leukaemic cytotoxicity showed a positive relationship in T cells, TCD4+ cells, TCD8+ cells and NKCD56+ cells.ConclusionsWe found blastmodulatory Kit-I and Kit-M competent to generate DC/DCleu from leukaemic WB. Stimulation of T cell enriched immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and an increased IFNy dependent immunological activity of T, NK and CIK cells compared to control. Moreover the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells. We therefore consider the IFNy secretion of innate and adaptive immune cells to be a suitable parameter to assess the efficacy of in vitro and potentially in vivo AML immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy secreting cells of the innate and adaptive immune system.Disclosure InformationL.K. Klauer: None. O. Schutti: None. S. Ugur: None. F. Doraneh-Gard: None. N. Rogers: None. M. Weinmann: None. D. Krämer: None. A. Rank: None. C. Schmid: None. B. Eiz-Vesper: None. H.M. Schmetzer: None.

scholarly journals Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Martin Solders ◽  
Laia Gorchs ◽  
Sebastian Gidlöf ◽  
Eleonor Tiblad ◽  
Anna-Carin Lundell ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Mait Cells ◽  
Adaptive Immune ◽  
Cell Compartments ◽  
Decidua Basalis ◽  
Adaptive Immune Cells ◽  
Cytotoxic Molecules ◽  
Multivariate Discriminant

The maternal part of the placenta, the decidua, consists of maternal immune cells, decidual stromal cells, and extravillous fetal trophoblasts. In a successful pregnancy, these cell compartments interact to provide an intricate balance between fetal tolerance and antimicrobial defense. These processes are still poorly characterized in the two anatomically different decidual tissues, basalis and parietalis. We examined immune cells from decidua basalis and parietalis from term placentas (n=15) with flow cytometry. By using multivariate discriminant analysis, we found a clear separation between the two decidual compartments based on the 81 investigated parameters. Decidua parietalis lymphocytes displayed a more activated phenotype with a higher expression of coinhibitory markers than those isolated from basalis and contained higher frequencies of T regulatory cells. Decidua basalis contained higher proportions of monocytes, B cells, and mucosal-associated invariant T (MAIT) cells. The basalis B cells were more immature, and parietalis MAIT cells showed a more activated phenotype. Conventional T cells, NK cells, and MAIT cells from both compartments potently responded with the production of interferon-γand/or cytotoxic molecules in response to stimulation. To conclude, leukocytes in decidua basalis and parietalis displayed remarkable phenotypic disparities, indicating that the corresponding stromal microenvironments provide different immunoregulatory signals.

scholarly journals Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell–Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction

2019 ◽  
Vol 26 (2) ◽  
pp. 229-241
Author(s):  
Deepa Rana Jamwal ◽  
Raji V Marati ◽  
Christy A Harrison ◽  
Monica T Midura-Kiela ◽  
Vanessa R Figliuolo Paz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Immunodeficient Mice ◽  
Cell Lineages ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been understudied, largely due to the lack of appropriate models. Methods We previously reported spontaneous colitis in mice with impaired TGFβ signaling due to dendritic cell–specific knockout of TGFbR2 (TGFβR2ΔDC). Here, we demonstrate that crossing TGFβR2ΔDC mice with a Rag1-/- background eliminates all symptoms of colitis and that adoptive transfer of unfractionated CD3+ splenocytes is sufficient to induce progressive colitis in Rag1-/-TGFβR2ΔDC mice. Results Both CD4+ and CD8+ T cells are required for the induction of colitis accompanied by activation of both T-cell lineages and DCs, increased expression of mucosal IFNγ, TNFα, IL6, IL1β, and IL12, and decreased frequencies of CD4+FoxP3+ regulatory T cells. Development of colitis required CD40L expression in CD4+ T cells, and the disease was partially ameliorated by IFNγ neutralization. Conclusions This novel model provides an important tool for studying IBD pathogenesis, in particular the complex interactions among innate and adaptive immune cells in a controlled fashion, and represents a valuable tool for preclinical evaluation of novel therapeutics.

scholarly journals Zika virus encephalitis in immunocompetent mice is dominated by innate immune cells and does not require T or B cells

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Emina Hayashida ◽  
Zheng Lung Ling ◽  
Thomas M. Ashhurst ◽  
Barney Viengkhou ◽  
So Ri Jung ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Immune Cells ◽  
Zika Virus ◽  
Innate Immune ◽  
Wild Type ◽  
Adaptive Immune ◽  
Intracranial Infection ◽  
Adaptive Immune Cells ◽  
Immunocompetent Mice

Abstract Background Until the end of the twentieth century, Zika virus (ZIKV) was thought to cause a mostly mild, self-limiting disease in humans. However, as the geographic distribution of ZIKV has shifted, so too has its pathogenicity. Modern-day ZIKV infection is now known to cause encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome in otherwise healthy adults. Nevertheless, the underlying pathogenetic mechanisms responsible for this shift in virulence remain unclear. Methods Here, we investigated the contribution of the innate versus the adaptive immune response using a new mouse model involving intracranial infection of adult immunocompetent mice with a moderately low dose of ZIKV MR766. To determine the contribution of type I interferons (IFN-Is) and adaptive immune cells, we also studied mice deficient for the IFN-I receptor 1 (Ifnar1−/−) and recombination-activating gene 1 (Rag1−/−). Results We show that intracranial infection with ZIKV resulted in lethal encephalitis. In wild-type mice, ZIKV remained restricted predominantly to the central nervous system (CNS) and infected neurons, whereas astrocytes and microglia were spared. Histological and molecular analysis revealed prominent activation of resident microglia and infiltrating monocytes that were accompanied by an expression of pro-inflammatory cytokines. The disease was independent of T and B cells. Importantly, unlike peripheral infection, IFN-Is modulated but did not protect from infection and lethal disease. Lack of IFN-I signaling resulted in spread of the virus, generalized inflammatory changes, and accelerated disease onset. Conclusions Using intracranial infection of immunocompetent wild-type mice with ZIKV, we demonstrate that in contrast to the peripheral immune system, the CNS is susceptible to infection and responds to ZIKV by initiating an antiviral immune response. This response is dominated by resident microglia and infiltrating monocytes and macrophages but does not require T or B cells. Unlike in the periphery, IFN-Is in the CNS cannot prevent the establishment of infection. Our findings show that ZIKV encephalitis in mice is dependent on the innate immune response, and adaptive immune cells play at most a minor role in disease pathogenesis.

scholarly journals Immune Vulnerability of Infants to Tuberculosis

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Koen Vanden Driessche ◽  
Alexander Persson ◽  
Ben J. Marais ◽  
Pamela J. Fink ◽  
Kevin B. Urdahl
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Immune Cells ◽  
Active Tuberculosis ◽  
Age Group ◽  
Older Children ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Disseminated Disease

One of the challenges faced by the infant immune system is learning to distinguish the myriad of foreign but nonthreatening antigens encountered from those expressed by true pathogens. This balance is reflected in the diminished production of proinflammatory cytokines by both innate and adaptive immune cells in the infant. A downside of this bias is that several factors critical for controllingMycobacterium tuberculosisinfection are significantly restricted in infants, including TNF, IL-1, and IL-12. Furthermore, infant T cells are inherently less capable of differentiating into IFN-γ-producing T cells. As a result, infected infants are 5–10 times more likely than adults to develop active tuberculosis (TB) and have higher rates of severe disseminated disease, including miliary TB and meningitis. Infant TB is a fundamentally different disease than TB in immune competent adults. Immunotherapeutics, therefore, should be specifically evaluated in infants before they are routinely employed to treat TB in this age group. Modalities aimed at reducing inflammation, which may be beneficial for adjunctive therapy of some forms of TB in older children and adults, may be of no benefit or even harmful in infants who manifest much less inflammatory disease.

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