scholarly journals Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Xing Liu ◽  
Shiyue Xu ◽  
Ying Li ◽  
Qian Chen ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
T Cells ◽  
Ischemic Cardiomyopathy ◽  
Mononuclear Cells ◽  
Gene Set Enrichment Analysis ◽  
Th2 Cells ◽  
Mrna Levels ◽  
Immune Infiltration ◽  
Diagnostic Values ◽  
Potential Biomarkers

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.

scholarly journals LncRNA PAXIP1-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Ovarian Cancer

2021 ◽  
Author(s):  
Buze Chen ◽  
Xiaoyuan Lu ◽  
Qingmei Zhou ◽  
Qing Chen ◽  
Siyan Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Th2 Cells ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
The Relationship

Abstract Background: The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. Methods: QRT-PCR, Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. Results: Low PAXIP1-AS1 expression in OC was associated with age (P=0.045), histological grade (P=0.011), and lymphatic invasion (P=0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55–0.92; P=0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067–2.955; P=0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51–0.89; P=0.006). And PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542-0.934; P=0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 may inhibit the function of aDC, B cells, CD8 T cells, Cytotoxic cells, DC, iDC, Macrophages, Mast cells, Neutrophils, NK CD56dim cells, T cells, TFH, Tgd, Th1 cells, Th2 cells and Treg. Conclusions: Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker for OC.

scholarly journals The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 101
Author(s):  
Ivet A. Yordanova ◽  
Friederike Ebner ◽  
Axel Ronald Schulz ◽  
Svenja Steinfelder ◽  
Berit Rosche ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Clinical Efficacy ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Th2 Cells ◽  
Continuous Increase ◽  
Trichuris Suis ◽  
Multiple Sclerosis Patients

Considering their potent immunomodulatory properties, therapeutic applications of Trichuris suis ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical phase 1 and 2 studies have demonstrated TSO treatment to be safe and well tolerated in MS patients, however, they reported only modest clinical efficacy. We therefore addressed the cellular and humoral immune responses directed against parasite antigens in individual MS patients receiving controlled TSO treatment (2500 TSO p.o. every 2 weeks for 12 month). Peripheral blood mononuclear cells (PBMC) of MS patients treated with TSO (n = 5) or placebo (n = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for T. suis excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DRhigh plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4+ and CD8+ T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR+CD4+ T cells in TSO-treated patients only. Frequencies of Gata3+ Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3+ Treg frequencies varied greatly between individuals. Using a T. suis antigen-specific T cell expansion assay, we also detected patient-to-patient variation of antigen-specific T cell recall responses and cytokine production. In summary, MS patients receiving TSO treatment established a T. suis-specific T- and B-cell response, however, with varying degrees of T cell responses and cellular functionality across individuals, which might account for the overall miscellaneous clinical efficacy in the studied patients.

Regulation of IL-17 in chronic inflammation in the human lung

2011 ◽  
Vol 120 (12) ◽  
pp. 515-524 ◽  
Author(s):  
Carol Pridgeon ◽  
Laurence Bugeon ◽  
Louise Donnelly ◽  
Ursula Straschil ◽  
Susan J. Tudhope ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Tissue ◽  
Mononuclear Cells ◽  
Human Lung ◽  
Treg Cells ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Chronic Obstructive ◽  
Interleukin 17

The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4+CD25+) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4+CD25+ T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4+CD25+ T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4+CD25+ T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.

scholarly journals APOC1 is a Potential Prognostic Biomarker and Correlated With Immune Infiltration in ESCC

2020 ◽  
Author(s):  
Jia-yi XIE ◽  
Ming Liu ◽  
Yaxin Luo ◽  
Zhen Wang ◽  
Zhenghong Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Killer Cell ◽  
Gene Set Enrichment Analysis ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract PurposeEsophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of EC. Identifying diagnostic biomarkers for ESCC is necessary for cancer practice. Increasing evidence illustrates that apolipoprotein C-1 (APOC1) participates in the carcinogenesis. However, the biological function of APOC1 in ESCC remains unclear. Patients and methodsWe investigated the expression level of APOC1 using TIMER2.0 and GEO databases, the prognostic value of APOC1 in ESCC using Kaplan-Meier plotter and TCGA databases. We used LinkedOmics to identify co-expressed genes with APOC1 and perform GO and KEGG pathway analysis. The target networks of kinases, miRNAs and transcription factors were predicted by gene set enrichment analysis (GSEA). The correlations between APOC1 and immune infiltration were calculated using TIMER2.0 and CIBERSORT databases. We further performed the prognostic analysis based on APOC1 expression levels in related immune cells subgroups via Kaplan-Meier plotter database. ResultsAPOC1 was found overexpressed in tumor tissues in multiple ESCC cohorts and high APOC1 expression was related to a dismal prognosis. Multivariate analysis confirmed that APOC1 overexpression was an independent indicator of poor OS. Functional network analysis indicated that APOC1 might regulate the natural killer cell mediated cytotoxicity, phagosome, AMPK and hippo signaling through pathways involving some cancer-related kinases, miRNA and transcription factors. Immune infiltration analysis showed that APOC1 was significantly positively correlated with M0 macrophages cells, M1 macrophages cells and activated NK cells, negatively correlated with regulatory T cells, CD8 T cells, neutrophils and monocytes. High APOC1 expression had a poor prognosis in server immune cells subgroups in ESCC, including decreased CD8+ T cells subgroups. ConclusionThese findings suggest that increased expression of APOC1 is related to poor prognosis and immune infiltration in ESCC. APOC1 holds promise for serving as a valuable diagnostic and prognostic marker in ESCC.

scholarly journals Constitutive Changes in Circulating Follicular Helper T Cells and Their Subsets in Patients with Graves’ Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yan Liu ◽  
Xinwang Yuan ◽  
Xiaofang Li ◽  
Dawei Cui ◽  
Jue Xie
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Graves Disease ◽  
Mrna Levels ◽  
Tfh Cells ◽  
Follicular Helper

Background. Follicular helper T (Tfh) cells are critical for high-affinity antibody generation and B cell maturation and differentiation, which play important roles in autoimmune diseases. Graves’ disease (GD) is one prototype of common organ-specific autoimmune thyroid diseases (AITD) characterized by autoreactive antibodies, suggesting a possible role for Tfh cells in the pathogenesis of GD. Our objective was to explore the role of circulating Tfh cell subsets and associated plasma cells (PCs) in patients with GD. Methods. Thirty-six patients with GD and 20 healthy controls (HC) were enrolled in this study. The frequencies of circulating Tfh cell subsets and PCs were determined by flow cytometry, and plasma cytokines, including interleukin- (IL-) 21, IL-4, IL-17A, and interferon- (IFN-) γ, were measured using an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of transcription factors (Bcl-6, T-bet, GATA-3, and RORγt) in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time quantitative PCR. Results. Compared with HC, the frequencies of circulating CD4+CXCR5+CD45RA−Tfh (cTfh) cells with ICOS and PD-1 expression, the Tfh2 subset (CXCR3−CCR6−Tfh) cells, and PCs (CD19+CD27highCD38high) were significantly increased in the GD patients, but the frequencies of Tfh1 (CXCR3+CCR6−Tfh) and Tfh17 (CXCR3−CCR6+Tfh) subset cells among CD4+T cells were significantly decreased in GD patients. The plasma concentrations of IL-21, IL-4, and IL-17A were elevated in GD patients. Additionally, a positive correlation was found between the frequency of PD-1+Tfh cells (Tfh2 or PCs) and plasma IL-21 concentration (or serum TPO-Ab levels). The mRNA levels of transcription factors (GATA-3 and RORγt) were significantly increased, but T-bet and Bcl-6 mRNA expression was not obviously varied in PBMCs from GD patients. Interestingly, Tfh cell subsets and PCs from GD patients were partly normalized by treatment. Conclusion. Circulating Tfh cell subsets and PCs might play an important role in the pathogenesis of GD, which are potential clues for GD patients’ interventions.

scholarly journals Identification of Key Immune-Related Genes, Molecular Pathways and Immune Infiltration as Diagnostic and Therapeutic Candidate Targets for RA: an integrated bioinformatics-based analysis

2021 ◽  
Author(s):  
Sheng Fang ◽  
Xiao Fang ◽  
Xin Xu ◽  
Lin Zhong ◽  
An-quan Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Mast Cells ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Systemic Autoimmune Disease ◽  
Molecular Pathways ◽  
Hub Genes ◽  
Immune Infiltration

Abstract Relevance Rheumatoid arthritis (RA) is a systemic autoimmune disease with an aggressive, chronic synovial inflammation as the main pathological change. However, the specific etiology, pathogenesis, and related biomarkers in diagnosis and treatment are still not fully elucidated. This study attempts to provide new perspectives and insights into RA at the genetic, molecular, and cellular levels through the tenet of personalized medicine. Methods Gene expression profiles of four individual knee synovial tissues were downloaded from a comprehensive gene expression database, R language was used to screen for significantly differentially expressed genes (DEGs), Gene Ontology Enrichment Analysis, Kyoto Gene Encyclopedia, and Gene Set Enrichment Analysis were performed to analyze the biological functions and signaling pathways of these DEGs, STRING online database was used to establish protein-protein interaction networks, Cytoscape software to obtain ten hub genes, Goplot to get six inflammatory immune-related hub genes, and CIBERSORT algorithm to impute immune infiltration. Results Molecular pathways that play important roles in RA were obtained: Toll-like receptors, AMPK, MAPK, TNF, FoxO, TGF-beta, PI3K and NF-κB pathways, Ten hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. among which Adcy2 and Pnoc have not been reported in RA studies, suggesting that they may be worthy targets for further study. It was also found that among the synoviocytes in RA, the proportions of plasma cells, CD8 T cells, follicular helper T cells, monocytes, γ delta T cells, and M0 macrophages were higher, while the proportions of CD4 memory resting T cells, regulatory T cells (Tregs), activated NK cells, resting dendritic cells, M1 macrophages, eosinophils, activated mast cells, resting mast cells were lower in proportion, and each cell played an important role in RA. Conclusions This study may help understand the key genes, molecular pathways, the role of inflammatory immune infiltrating cells in RA’s pathogenesis and provide new targets and ideas for the diagnosis and personalized treatment of RA.

scholarly journals An Integrative Pan-Cancer Analysis Revealing LCN2 as an Oncogenic Immune Protein in Tumor Microenvironment

2020 ◽  
Vol 10 ◽  
Author(s):  
Wen-Xiu Xu ◽  
Jian Zhang ◽  
Yu-Ting Hua ◽  
Su-Jin Yang ◽  
Dan-Dan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cytochrome P450 ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Sterile Inflammation ◽  
Lipocalin 2 ◽  
Immune Infiltration ◽  
Pan Cancer

BackgroundLipocalin 2 (LCN2), an innate immune protein, plays a pivotal role in promoting sterile inflammation by regulating immune responses. However, the role of LCN2 in diverse cancers remains poorly defined. This research aimed to investigate the correlation between LCN2 expression and immunity and visualize its prognostic landscape in pan-cancer.MethodsRaw data in regard to LCN2 expression in cancer patients were acquired from TCGA and GTEx databases. Besides, we investigated the genomic alterations, expression pattern, and survival analysis of LCN2 in pan-cancer across numerous databases, including cBioPortal and GEPIA database. The correlation between LCN2 expression and tumor immune infiltration was explored via TIMER, and we utilized CIBERSORT and ESTIMATE computational methods to assess the proportion of tumor-infiltrating immune cells (TIICs) and the amount of stromal and immune components from TCGA database. Protein–Protein Interaction analysis was performed in GeneMANIA database, and gene functional enrichment was performed by Gene Set Enrichment Analysis (GSEA).ResultsOn balance, tumor tissue had a higher LCN2 expression level compared with that in normal tissue. Elevated expression of LCN2 was related to poor clinical regimen with OS and RFS. There were significant positive correlations between LCN2 expression and TIICs, including CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Moreover, markers of TIICs exhibited different LCN2-related immune infiltration patterns. GSEA analysis showed that the expression of LCN2 was related to retinol metabolism, drug metabolism cytochrome P450 and metabolism of xenobiotics by cytochrome P450.ConclusionsThese findings suggested that LCN2 might serve as a biomarker for immune infiltration and poor prognosis in cancers, shedding new light on therapeutics of cancers.

Association of Th2 high tumors with aggressive features of breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12584-e12584
Author(s):  
Yoshihisa Tokumaru ◽  
Lan Le ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Th2 Cells ◽  
Immune Microenvironment ◽  
Adaptive Immune Cells ◽  
Tumor Immune Microenvironment

e12584 Background: Recent studies have shown that infiltrating T-lymphocytes have been implicated in the promotion of breast cancer progression. Upon activation, these antigen-presenting cells then recruit adaptive immune cells. It has been proposed that polarization of CD4+ effector T-cells towards the immunosuppressive Th2 cells induce cytokine release and T-cell anergy, which lead to polarization of M2 tumor-associated macrophages (TAM’s), providing a protumorigenic microenvironment. We hypothesized that there is a correlation between high levels of Th2 cells and aggressive features of breast cancer and unfavorable tumor immune environment. Methods: Clinicopathological data and overall survival information was obtained on 1069 breast cancer patients from The Cancer Genome Atlas (TCGA) database. We defined Th2 high and low levels with the median cutoff. Results: Analysis of cell composition of the immune cells within tumor immune microenvironment demonstrated that Th2 high tumors did not consistently associated with unfavorable tumor immune microenvironment. Pro-cancer immune cells, such as macrophage M2 cells were increased with Th2 high tumors whereas, regulatory T cells were decreased with Th2 high tumors (p < 0.01 and p < 0.001 respectively). On the contrary, infiltration of anti-cancer cells, such as macrophage M1 was increased whereas CD8 T cells were decreased with Th2 high tumors (p < 0.05 and p < 0.001 respectively). Th2 was not shown to have correlation with IL-4, IL-6, IL-10 and IL-13, all of which has been reported to associate with Th2 cells. Th2 levels were associated with advanced grades. Also, correlation analysis demonstrated that there was a strong correlation between Th2 levels and Ki-67. These results were further validated with gene set enrichment analysis (GSEA). GSEA revealed that in Th2 high tumors enriched the gene sets associated with cell proliferation and cell cycle. Conclusions: High expression of immunosuppressive Th2 cells was associated with highly proliferative features of breast cancer, but not with unfavorable tumor immune microenvironment.

scholarly journals IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 346-356 ◽  
Author(s):  
Mark A. Brockman ◽  
Douglas S. Kwon ◽  
Daniel P. Tighe ◽  
David F. Pavlik ◽  
Pamela C. Rosato ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Cell Types ◽  
Interleukin 10 ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Multiple Cell

AbstractMurine models indicate that interleukin-10 (IL-10) can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T-cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is up-regulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (NK) cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and -uninfected individuals. These data indicate that multiple cell types contribute to IL-10–mediated immune suppression in the presence of uncontrolled HIV viremia.

scholarly journals Resistance of CD7-deficient Mice to Lipopolysaccharide-induced Shock Syndromes

1999 ◽  
Vol 189 (6) ◽  
pp. 1011-1016 ◽  
Author(s):  
Gregory D. Sempowski ◽  
David M. Lee ◽  
Richard M. Scearce ◽  
Dhavalkumar D. Patel ◽  
Barton F. Haynes
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Immunoglobulin Superfamily ◽  
High Dose ◽  
Mrna Levels ◽  
Lps Challenge ◽  
Tnf Α ◽  
Ifn Γ ◽  
Deficient Mice

CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-γ production and CD8+ CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-γ, the response of CD7-deficient mice to lipopolysaccharide (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control C57BL/6 mice survived LPS challenge (P &lt; 0.001). CD7-deficient or C57BL/6 control mice were next injected with low-dose LPS (1 μg plus 8 mg D-galactosamine [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive 72 h after injection of LPS compared with 20% of C57BL/6 control mice (P &lt; 0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum IFN-γ and tumor necrosis factor (TNF)-α levels compared with control C57BL/6 mice (P &lt; 0.001). Steady-state mRNA levels for IFN-γ and TNF-α in liver tissue were also significantly decreased in CD7-deficient mice compared with controls (P &lt; 0.05). In contrast, CD7-deficient animals had normal liver interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA levels, and CD7-deficient splenocytes had normal IFN-γ responses when stimulated with IL-12 and IL-18 in vitro. NK1.1+/ CD3+ T cells are known to be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of liver NK1.1+/CD3+ T cells (1.5 ± 0.3 × 105) versus C57BL/6 control mice (3.7 ± 0.8 × 105; P &lt; 0.05), whereas numbers of liver NK1.1+/CD3− NK cells were not different from controls. Thus, targeted disruption of CD7 leads to a selective deficiency of liver NK1.1+/ CD3+ T cells, and is associated with resistance to LPS shock. These data suggest that CD7 is a key molecule in the inflammatory response leading to LPS-induced shock.

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