scholarly journals Early Response of CD8+ T Cells in COVID-19 Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
Deni Ramljak ◽  
Martina Vukoja ◽  
Marina Curlin ◽  
Katarina Vukojevic ◽  
Maja Barbaric ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Effector Memory ◽  
Healthy Controls ◽  
Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
A Hug ◽  
J Haas ◽  
A Viehöver ◽  
B Fritz ◽  
B Storch-Hagenlocher ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Effector T Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals The effect of Kefir on The Immune Response of Healthy Volunteers In Vitro

2017 ◽  
Vol 3 (2) ◽  
pp. 28
Author(s):  
Desie Dwi Wisudanti
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Fermented Milk ◽  
Bioactive Components ◽  
Ifn Γ

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.

scholarly journals Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques

2015 ◽  
Vol 22 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
A. D. White ◽  
C. Sarfas ◽  
K. West ◽  
L. S. Sibley ◽  
A. S. Wareham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bcg Vaccine ◽  
Effector Memory ◽  
Dependent Manner ◽  
Aerosol Delivery ◽  
Memory Phenotype ◽  
Bcg Vaccination

ABSTRACTNine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, theMycobacterium bovisBCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4β1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung.

scholarly journals Aortic Gene Expression Profiles Show How ApoA-I Levels Modulate Inflammation, Lysosomal Activity, and Sphingolipid Metabolism in Murine Atherosclerosis

2020 ◽  
Author(s):  
Marco Busnelli ◽  
Stefano Manzini ◽  
Matteo Chiara ◽  
Alice Colombo ◽  
Fabrizio Fontana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Sphingolipid Metabolism ◽  
Gene Expression Patterns ◽  
Peripheral Tissues ◽  
Lysosomal Activity ◽  
Better Regulation ◽  
Atherosclerosis Development

Objective: HDL (high-density lipoprotein) particles are known to possess several antiatherogenic properties that include the removal of excess cholesterol from peripheral tissues, the maintenance of endothelial integrity, antioxidant, and anti-inflammatory activities. ApoA-I overexpression in apoE-deficient (EKO) mice has been shown to increase HDL levels and to strongly reduce atherosclerosis development. The aim of the study was to investigate gene expression patterns associated with atherosclerosis development in the aorta of EKO mice and how HDL plasma levels relate to gene expression patterns at different stages of atherosclerosis development and with different dietary treatments. Approach and Results: Eight-week-old EKO mice, EKO mice overexpressing human apoA-I, and wild-type mice as controls were fed either normal laboratory or Western diet for 6 or 22 weeks. Cholesterol distribution among lipoproteins was evaluated, and atherosclerosis of the aorta was quantified. High-throughput sequencing technologies were used to analyze the transcriptome of the aorta of the 3 genotypes in each experimental condition. In addition to the well-known activation of inflammation and immune response, the impairment of sphingolipid metabolism, phagosome-lysosome system, and osteoclast differentiation emerged as relevant players in atherosclerosis development. The reduced atherosclerotic burden in the aorta of EKO mice expressing high levels of apoA-I was accompanied by a reduced activation of immune system markers, as well as reduced perturbation of lysosomal activity and a better regulation of the sphingolipid synthesis pathway. Conclusions: ApoA-I modulates atherosclerosis development in the aorta of EKO mice affecting the expression of pathways additional to those associated with inflammation and immune response.

scholarly journals The differential production of cytokines by human Langerhans cells and dermal CD14+ DCs controls CTL priming

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5742-5749 ◽  
Author(s):  
Jacques Banchereau ◽  
LuAnn Thompson-Snipes ◽  
Sandra Zurawski ◽  
Jean-Philippe Blanck ◽  
Yanying Cao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Langerhans Cells ◽  
Expression Profiles ◽  
Cd8 T Cell ◽  
Inhibitory Effect ◽  
Effector Memory ◽  
Functional Difference ◽  
T Cell Priming

Abstract We recently reported that human epidermal Langerhans cells (LCs) are more efficient than dermal CD14+ DCs at priming naive CD8+ T cells into potent CTLs. We hypothesized that distinctive dendritic cell (DC) cytokine expression profiles (ie, IL-15 produced by LCs and IL-10 expressed by dermal CD14+ DCs) might explain the observed functional difference. Blocking IL-15 during CD8+ T-cell priming reduced T-cell proliferation by ∼ 50%. These IL-15–deprived CD8+ T cells did not acquire the phenotype of effector memory cells. They secreted less IL-2 and IFN-γ and expressed only low amounts of CD107a, granzymes and perforin, and reduced levels of the antiapoptotic protein Bcl-2. Confocal microscopy analysis showed that IL-15 is localized at the immunologic synapse of LCs and naive CD8+ T cells. Conversely, blocking IL-10 during cocultures of dermal CD14+ DCs and naive CD8+ T cells enhanced the generation of effector CTLs, whereas addition of IL-10 to cultures of LCs and naive CD8+ T cells inhibited their induction. TGF-β1 that is transcribed by dermal CD14+ DCs further enhanced the inhibitory effect of IL-10. Thus, the respective production of IL-15 and IL-10 explains the contrasting effects of LCs and dermal CD14+ DCs on CD8+ T-cell priming.

The HaemAtlas: Characterising Gene Expression in Differentiated Human Blood Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2453-2453
Author(s):  
Nicholas A. Watkins ◽  
Marloes R. Tijssen ◽  
Arief Gusnanto ◽  
Bernard de Bono ◽  
Subhajyoti De ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Cell Function ◽  
Expression Profiles ◽  
Association Studies ◽  
Cytotoxic T Cells ◽  
Expression Patterns ◽  
Immunoglobulin Superfamily ◽  
Genome Wide Association Studies

Abstract Haematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell surface receptors. In order to further understand haematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B-cells, cytotoxic and helper T-cells, Natural Killer cells, granulocytes and monocytes using whole genome microarrays. A bioinformatics analysis of this data was performed focusing on transcription factors, immunoglobulin superfamily members and lineage specific transcripts. We observed that the numbers of lineage specific genes varies by two orders of magnitude, ranging from five for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel co-expression patterns for key transcription factors involved in haematopoiesis (eg. GATA3–GFI1 and GATA2–KLF1). This study represents the most comprehensive analysis of gene expression in haematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which is freely accessible, will be invaluable for future studies on haematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

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

Aging Cell ◽  
2010 ◽  
Vol 9 (1) ◽  
pp. 19-31 ◽  
Author(s):  
Jia-Ning Cao ◽  
Sastry Gollapudi ◽  
Edward H. Sharman ◽  
Zhenyu Jia ◽  
Sudhir Gupta
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Age Related

scholarly journals Comprehensive Analysis of Cell Population Dynamics and Related Core Genes During Vitiligo Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingzhan Zhang ◽  
Shirong Yu ◽  
Wen Hu ◽  
Man Wang ◽  
Dilinuer Abudoureyimu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Healthy Controls ◽  
Cell Abundance

Vitiligo is a common immune-related depigmentation condition, and its pathogenesis remains unclear. This study used a combination of bioinformatics methods and expression analysis techniques to explore the relationship between immune cell infiltration and gene expression in vitiligo. Previously reported gene expression microarray data from the skin (GSE53146 and GSE75819) and peripheral blood (GSE80009 and GSE90880) of vitiligo patients and healthy controls was used in the analysis. R software was used to filter the differentially expressed genes (DEGs) in each dataset, and the KOBAS 2.0 server was used to perform functional enrichment analysis. Compared with healthy controls, the upregulated genes in skin lesions and peripheral blood leukocytes of vitiligo patents were highly enriched in immune response pathways and inflammatory response signaling pathways. Immunedeconv software and the EPIC method were used to analyze the expression levels of marker genes to obtain the immune cell population in the samples. In the lesional skin of vitiligo patients, the proportions of macrophages, B cells and NK cells were increased compared with healthy controls. In the peripheral blood of vitiligo patients, CD8+ T cells and macrophages were significantly increased. A coexpression analysis of the cell populations and DEGs showed that differentially expressed immune and inflammation response genes had a strong positive correlation with macrophages. The TLR4 receptor pathway, interferon gamma-mediated signaling pathway and lipopolysaccharide-related pathway were positively correlated with CD4+ T cells. Regarding immune response-related genes, the overexpression of IFITM2, TNFSF10, GZMA, ADAMDEC1, NCF2, ADAR, SIGLEC16, and WIPF2 were related to macrophage abundance, while the overexpression of ICOS, GPR183, RGS1, ILF2 and CD28 were related to CD4+ T cell abundance. GZMA and CXCL10 expression were associated with CD8+ T cell abundance. Regarding inflammatory response-related genes, the overexpression of CEBPB, ADAM8, CXCR3, and TNIP3 promoted macrophage infiltration. Only ADORA1 expression was associated with CD4+ T cell infiltration. ADAM8 and CXCL10 expression were associated with CD8+ T cell abundance. The overexpression of CCL18, CXCL10, FOS, NLRC4, LY96, HCK, MYD88, and KLRG1, which are related to inflammation and immune responses, were associated with macrophage abundance. We also found that immune cells infiltration in vitiligo was associated with antigen presentation-related genes expression. The genes and pathways identified in this study may point to new directions for vitiligo treatment.

scholarly journals Tracking Effector T Cell Dynamics and Immune Inhibitory Receptors in Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3849-3849
Author(s):  
Hanna A. Knaus ◽  
Raúl Montiel-Esparza ◽  
Joshua F. Zeidner ◽  
Amanda Blackford ◽  
Christopher G. Kanakry ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
T Cell Differentiation ◽  
Effector Memory ◽  
Inhibitory Receptors ◽  
Cell Dynamics ◽  
Effector T Cell

Abstract Background: Targeting specific immune inhibitory receptors (iRs) with monoclonal antibodies has led to paradigm-shifting treatment practices in a variety of solid cancers. These advances were in part driven by tremendous progress in phenotypic and functional characterization of altered iR expression patterns and memory T cell differentiation states such as exhaustion and senescence. Effector T cell dynamics and iR expression patterns in AML patients (pts) at diagnosis and after induction chemotherapy are not well understood and, if deciphered, are poised to be critically important for optimal integration of therapeutic blockade of various iRs in the clinic. Methods: We analyzed T cell dynamics and iR expression in peripheral blood (PB, n=45) and bone marrow (BM, n=38) cells from 49 pts (median age 60, range 21-76) with newly diagnosed AML. After induction, 36 (73%) pts entered complete remission (CR) whereas 13 (27%) were non responders (NR). Samples were collected at diagnosis, upon recovery after induction and following consolidation/salvage chemotherapy. Using multi-parameter flow cytometry, we characterized the differentiation status (CD45RA, CCR7), and the expression of co-stimulatory receptors (CD27, CD28) and iRs. Our gating strategy excluded NK T cells (CD3+ CD56+) from downstream analyses. Co-expression of iRs was analyzed in combination of 3 (2B4, BTLA, TIM3) or 4 (KLRG-1, CD57, PD-1 and CD160) markers. As a control, we used PB (n=41)/BM (n=16) lymphocytes from healthy controls (HC). Percentage of cells expressing specific markers were log transformed and modeled with mixed-effect linear regression models. Differential response outcomes over time were tested with interaction terms. Co-expression of multiple iRs was also analyzed with SPICE software version 5.3. Results: At diagnosis, AML pts showed significantly lower median frequency of CD8+ naïve (CD45RA+ CCR7+) T cells in PB, but higher frequencies of terminal differentiated effector memory (TEMRA; CD45RA+ CCR7-) and phenotypically senescent CD8+ CD27- CD28- CD57+ T cells. Significantly higher percentages of PB CD4+ and CD8+ T cells were found to express PD1 and 2B4 compared to HC. Additionally, the frequency of PB CD8+ T cells co-expressing 2-4 iRs was significantly higher in the PB of AML pts (Fig.1). Surprisingly, in contrast to PB, the only significant finding in the BM of AML pts at diagnosis was increased frequency of CD8+ CD27- CD28- CD57+ T cells (p<0.001) compared to HC. At the time of hematopoietic recovery from chemotherapy, TEMRAs and CD8+ CD27- CD28- CD57+ T cells significantly decreased in PB and BM of AML pts, compared to pretreatment levels. However, if analyzed by response, frequencies of these populations declined only in CR pts (p<0.001), but remained unchanged in NR pts. Analysis of iR co-expression in relation to the response to chemotherapy and time revealed that the frequency of CD8+ T cells co-expressing multiple IRs decreases in CR pts but increases in NR pts. These response-associated changes in iR co-expression were observed only in BM while, in PB, the iR co-expression profile remained unchanged irrespective of response. Finally, we assessed the effect of diverse pre-treatment factors on T cell composition at AML diagnosis. We found that older age was associated with increased frequency of CD8+ T cells expressing the iR marker KLRG-1 and the senescent T cell phenotype CD8+ CD27- CD28- CD57+ (p<0.001) but age did not affect iR co-expression on T cells in either PB or BM. CMV seropositivity was associated with increased CD8+ TEMRAs in PB and CD8+ T cells co-expressing multiple iRs (mostly Tim3 and 2B4) in both compartments. The effect of sex, cytogenetic risk group, or ELN category was insignificant. Conclusion: Our study provides critical insights into T cell differentiation and iR expression at diagnosis and during the course of treatment in pts with AML. We have identified several dominant expression patterns suggesting that iR signatures are consistent with immune recognition of AML and their role in sculpting the effector T cell responses directed against AML cell populations. However, data need to be interpreted in the context of the anatomical compartment and non-inheritable variables such as CMV and age. While ongoing work is focused on the deciphering significance of IRs expression for the interpretation of T cell functionality, our data support the rationale for therapeutic blocking of iRs in AML. Disclosures No relevant conflicts of interest to declare.

scholarly journals Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

2020 ◽  
Author(s):  
Hasi Chaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Circulating Cytokines

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

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