scholarly journals Gene Expression Patterns Associated with Tumor-Infiltrating CD4+ and CD8+ T Cells in Invasive Breast Carcinomas

2020 ◽  
Author(s):  
zhanwei Wang ◽  
Jiamin Xu ◽  
Xi Yang ◽  
Yuefen Pan ◽  
Junjun Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Gene Expression Patterns ◽  
Breast Carcinomas ◽  
Invasive Breast Carcinomas ◽  
Immune Score

Abstract Objective: This study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.Methods: The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results: In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes.Conclusions: The chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.

scholarly journals Gene Expression Patterns Associated With Tumor-Infiltrating CD4+ and CD8+ T Cells In Invasive Breast Carcinomas

2020 ◽  
Author(s):  
Zhanwei Wang ◽  
Jiamin Xu ◽  
Xi Yang ◽  
Yuefen Pan ◽  
Junjun Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Gene Expression Patterns ◽  
Breast Carcinomas ◽  
Invasive Breast Carcinomas ◽  
Immune Score

Abstract Objective This study investigated the gene expression patterns associated with tumor-infiltrating CD4 + and CD8 + T cells in invasive breast carcinomas.Methods The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4 + and CD8 + T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4 + T cell-related genes and 78 CD8 + T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4 + T cell-related genes, the chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8 + T cell-related genes.Conclusions The chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4 + and CD8 + T cell infiltration, respectively, in BRCA.

Gene Expression Patterns Associated With Tumor-infiltrating CD4+  and CD8+ T Cells in Invasive Breast Carcinomas 

2020 ◽  
Author(s):  
Zhanwei Wang ◽  
Xi Yang ◽  
Jiamin Xu ◽  
Yuefen Pan ◽  
Junjun Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Gene Expression Patterns ◽  
Cerna Network ◽  
Immune Score

Abstract Objective: This study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.Methods: The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results: In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes.Conclusions: The chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.

Significant Decreased in Cord Blood (CB) Versus Adult Peripheral Blood (APB) Monocyte (Mo)-Derived Dendritic Cells (DC) Gene Expression Patterns and T Cell Functional Activation: Insight into Immaturity of CB Cellular Immunity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2210-2210
Author(s):  
H. Jiang ◽  
C. Wade-Harris ◽  
L. Baxi ◽  
M. S. Cairo
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
T Cell ◽  
Cd8 T Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Surface Molecules ◽  
Transcription Factor Genes ◽  
Presentation Activity

Abstract It has been recognized that dysfunction of CB immunity is in part due to the immaturity of the neonatal immune system (Cairo, Blood, 1997). However, biological pathways and molecular mechanisms associated with the immaturity of CB immunity are still poorly understood. Recently we have utilized oligonucleotide microarray to examine gene expression profiling of CB versus APB Mo and have demonstrated significant differential gene expression patterns, including surface molecules, cytokines, signaling molecules, transcription factors and apoptotic genes (Jiang/Cairo, et al, J. of Immunol., 2004). We sought to examine whether there are differential expressed genes occurred in Mo-derived CB versus APB DC and their impact on DC mediated T cell activity. Briefly, Mo were purified from fresh CB or APB and cultured for 8 days with GM-CSF and IL-4 (immature DC (iDC)) and LPS for mature DC (mDC). mRNA was isolated and oligonucleotide microarray was carried out (Affymetrix, U133A). Data was analyzed by Microarray Suite Version 5.0 (Affymetrix) and GeneSpring 5.0 software (Silicon Genetics). Selected genes were analyzed by RT-PCR (SuperScript, Invetrogen). We identified gene expression patterns that were significantly lower in CB versus APB DC including surface molecules HLA-DQA1 (4F), HLA-DRB3 (5F), HLA-DRB4 (5.5F), CD80 (3F), CD38 (3.8F); cytokine/chemokine genes IL-1b (2.5F), IL6 (2.9F), IL12B (3.5F), CXCL10 (6.6F); immunoregulatory genes ISG20 (11F), IFI27 (7.6F), TNFSF10 (4.5F), SOCS3 (2.5F). Moreover, several transcription factor genes whose proteins may involve in the activation of expression of these immune regulator genes were also differentially expressed (IRF-5 (3F), IRF7 (3F), MAD (6.3F)). We therefore compared CB versus APB DC antigen presentation activity to APB CD8 T cells by ELISPOT assay for interferon-r (IFNr) production (BD Pharmagen). Briefly, the purified CD8 T cells (MHC HLA A2) were incubated with CB or APB DC that were loaded without or with influenza peptide onto ELISPOT plate (Larsson, et al, J. of Immunol., 2000). The ELISPOT plates were developed, scanned and quantitated by an ELISPOT reader (C.T.L. Technology). Our results demonstrated that, although CB or APB mDC had allogeneic effects, influenza peptide loaded CB mDC was not able to induce CD8 T cells to produce IFNr while APB mDC loaded with influenza peptide strongly induced CD8 T cells to produce IFNr. This stimulatory effect of APB mDC on CD8 T cells to produce IFNr was 3.5 fold greater than that of CB mDC. We further examined DC antigen presentation activity to CD4 T cells and observed that APB-DC had stronger effects on CD4 T cell proliferation (3 fold for mDC vs. iDC) compared with CB-DC (only 1.5 fold for mDC vs. iDC) by CFSE assay (Molecular Probe). We postulate that decreased expression of specific surface molecules and other genes resulting in lower surface protein expression in CB DC may in part be responsible for the lack of initiation of signaling events from cell surface to trigger CB-DC to stimulate activation of CD8 and CD4 T cells. The decreased expression of transcription factor genes may also in part be responsible for the lower expressed surface molecule genes. Furthermore, these decreased expressed genes in other molecular categories in LPS-CB vs. APB DC may also partially be responsible for differential innate and adaptive immune function and properties of CB vs. APB.

scholarly journals Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis

2019 ◽  
Vol 5 (3) ◽  
pp. 63
Author(s):  
Alice Bayiyana ◽  
Samuel Okurut ◽  
Rose Nabatanzi ◽  
Godfrey Zziwa ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Cryptococcal Meningitis ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Subset

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.

scholarly journals Unique Gene Expression Patterns in Human T-cell Lines Generated from Multiple Sclerosis Patients by Stimulation with a Synthetic MOG Peptide

2005 ◽  
Vol 12 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Mathilda Mandel ◽  
Michael Gurevich ◽  
Gad Lavie ◽  
Irun R. Cohen ◽  
Anat Achiron
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Healthy Subjects ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Gene Expression Patterns ◽  
T Cell Lines ◽  
Myelin Antigens

Multiple sclerosis (MS) is an autoimmune disease where T-cells activated against myelin antigens are involved in myelin destruction. Yet, healthy subjects also harbor T-cells responsive to myelin antigens, suggesting that MS patient-derived autoimmune T-cells might bear functional differences from T-cells derived from healthy individuals. We addressed this issue by analyzing gene expression patterns of myelin oligodendrocytic glycoprotein (MOG) responsive T-cell lines generated from MS patients and healthy subjects. We identified 150 transcripts that were differentially expressed between MS patients and healthy controls. The most informative 43 genes exhibited >1.5-fold change in expression level. Eighteen genes were up-regulated including BCL2, lifeguard, IGFBP3 and VEGF. Twenty five genes were down-regulated, including apoptotic activators like TNF and heat shock protein genes. This gene expression pattern was unique to MOG specific T-cell lines and was not expressed in T-cell lines reactive to tetanus toxin (TTX). Our results indicate that activation in MS that promotes T-cell survival and expansion, has its own state and that the unique gene expression pattern that characterize autoreactive T-cells in MS represent a constellation of factors in which the chronicity, timing and accumulation of damage make the difference between health and disease.

scholarly journals Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

2021 ◽  
Author(s):  
Suhas Sureshchandra ◽  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Allen Jankeel ◽  
Izabela Ibraim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Natural Infection ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

scholarly journals Fas-mediated apoptosis of CD4+ and CD8+ T cells from human immunodeficiency virus-infected persons: differential in vitro preventive effect of cytokines and protease antagonists

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 4959-4966 ◽  
Author(s):  
J Estaquier ◽  
M Tanaka ◽  
T Suda ◽  
S Nagata ◽  
P Golstein ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Death Process ◽  
T Cell Apoptosis ◽  
Soluble Fas ◽  
Immunodeficiency Syndrome

Human immunodeficiency syndrome (HIV) infection leads to a progressive loss of T-cell-mediated immunity associated with T-cell apoptosis. We report here that CD4+ and CD8+ T cells from HIV-1-infected persons are sensitive to Fas (CD95/APO-1)-mediated death induced either by an agonistic anti-Fas antibody or by the physiologic soluble Fas ligand, although showing no sensitivity to tumor necrosis factor alpha-induced death. CD4+ and CD8+ T-cell apoptosis induced by Fas ligation was enhanced by inhibitors of protein synthesis and was prevented either by a soluble Fas receptor decoy or an antagonistic anti-Fas antibody. Fas- mediated apoptosis could also be prevented in a CD4+ or CD8+ T-cell- type manner (1) by several protease antagonists, suggesting the involvement of the interleukin-1beta (IL-1beta)-converting enzyme (ICE)- related cysteine protease in CD4+ T-cell death and of both a CPP32- related cysteine protease and a calpain protease in CD8+ T-cell death; and (2) by three cytokines, IL-2, IL-12, and IL-10, that exerted their effects through a mechanism that required de novo protein synthesis. Finally, T-cell receptor (TCR)-induced apoptosis of CD4+ T cells from HIV-infected persons involved a Fas-mediated death process, whereas TCR stimulation of CD8+ T cells led to a different Fas-independent death process. These findings suggest that Fas-mediated T-cell death is involved in acquired immunodeficiency syndrome (AIDS) pathogenesis and that modulation of Fas-mediated signaling may represent a target for new therapeutic strategies aimed at the prevention of CD4+ T-cell death in AIDS.

Gene expression patterns distinguish breast carcinomas from normal breast tissues: The Malaysian context

2010 ◽  
Vol 206 (4) ◽  
pp. 223-228 ◽  
Author(s):  
Ivyna Bong Pau Ni ◽  
Zubaidah Zakaria ◽  
Rohaizak Muhammad ◽  
Norlia Abdullah ◽  
Naqiyah Ibrahim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Normal Breast ◽  
Gene Expression Patterns ◽  
Breast Carcinomas ◽  
Breast Tissues

T Cell Recognition of HCMV: Pan-Genome Analysis of Immunogenic Open-Reading Frames.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 606-606 ◽  
Author(s):  
Louis J. Picker ◽  
Andrew W. Sylwester ◽  
Bridget L. Mitchell ◽  
Cara Taormina ◽  
Christian Pelte ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses

Abstract Human Cytomegalovirus (HCMV) is among the largest and most complex of known viruses with 150–200nm virions enclosing a double stranded 230kb DNA genome capable of coding for >200 proteins. HCMV infection is life-long, and for the vast majority of immune competent individuals clinically benign. Disease occurs almost exclusively in the setting of immune deficiency, suggesting that the stable host-parasite relationship that characterizes these infections is the result of an evolutionarily “negotiated” balance between viral mechanisms of pathogenesis and the host immune response. In keeping with, and perhaps because of this balance, the human CD4+ T cell response to whole HCMV viral lysates is enormous, with median peripheral blood frequencies of HCMV-specific cells ~5–10 fold higher than for analogous preparations of other common viruses. Although certain HCMV ORFs have been identified as targets of either the CD4+ or CD8+ T cell response, the specificities comprising the CD4+ T cell response, and both the total frequencies and component parts of the CD8+ T cell response are unknown. Here, we used cytokine flow cytometry and ~14,000 overlapping 15mer peptides comprising all 213 HCMV ORFs encoding proteins >100 amino acids in length to precisely define the total CD4+ and CD8+ HCMV-specific T cell responses and the HCMV ORFs responsible for these responses in 33 HCMV-seropositive, HLA-disparate donors. An additional 9 HCMV seronegative donors were similarly examined to define the extent to which non-HCMV responses cross-react with HCMV-encoded epitopes. We found that when totaled, the median frequencies of HCMV-specific CD4+ and CD8+ T cells in the peripheral blood of the seropositive subjects were 4.0% and 4.5% for the total CD4+ or CD8+ T cell populations, respectively (which corresponds to 9.1% and 10.5% of the memory populations, respectively). The HCMV-specific CD4+ and CD8+ T cell responses included a median 12 and 7 different ORFs, respectively, and all told, 73 HCMV ORFs were identified as targets for both CD4+ and CD8+ T cells, 26 ORFs as targets for CD8+ T cells alone, and 43 ORFS as targets for CD4+ T cells alone. UL55, UL83, UL86, UL99, and UL122 were the HCMV ORFs most commonly recognized by CD4+ T cells; UL123, UL83, UL48, UL122 and UL28 were the HCMV ORFs most commonly recognized by CD8+ T cells. The relationship between immunogenicity and 1) HLA haplotype and 2) ORF expression and function will be discussed. HCMV-seronegative individuals were non-reactive with the vast majority of HCMV peptides. Only 7 potentially cross-reactive responses were identified (all by CD8+ T cells) to 3 ORFs (US32, US29 and UL116) out of a total of almost 4,000 potential responses, suggesting fortuitous cross-reactivity with HCMV epitopes is uncommon. These data provide the first glimpse of the total human T cell response to a complex infectious agent, and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.

Sign in / Sign up

Export Citation Format

Share Document