Phenotype, Function, and Gene Expression Profiles of Programmed Death-1hi CD8 T Cells in Healthy Human Adults

Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

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Donor T Cell Gene Expression and GVHD.

Blood ◽

10.1182/blood.v112.11.sci-53.sci-53 ◽

2008 ◽

Vol 112 (11) ◽

pp. sci-53-sci-53

Author(s):

Claude Perreault

Keyword(s):

Gene Expression ◽

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Expression Profiling ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Qrt Pcr ◽

One Year ◽

Donor Gene

GVHD is initiated by donor T cell responses to host alloantigens. However, the occurrence and severity of GVHD are not determined solely by the level of histoincompatibility between donor and recipient. Two MHC-identical subjects will display over 50 minor histocompatibility antigen differences. If histoincompatibility is sufficient for triggering GVHD, the rate of GVHD in MHC-matched recipients of allogeneic hematopoietic cell transplantation (HCT) that receive no immunosuppressive agents should be 100%. Under these conditions, however, GVHD is found in only 50% and 73% of mouse and human recipients, respectively. Histoincompatibility is thus necessary but not sufficient to elicit GVHD. We tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD. To this end, we studied the gene expression profiles of CD4 and CD8 T cells from 50 HCT donors using microarrays and qRT-PCR. We found that gene expression profiling before HCT was able to distinguish those donors whose cells caused GVHD from those whose cells did not. The “dangerous donor” trait (GVHD+ recipient) is under polygenic control and is shaped by the activity of genes that regulate TGF-β signaling and cell proliferation. The donor gene profile defined on day 0 shows strong correlation with that of recipient CD4 and CD8 T cells harvested one year post-AHCT. The latter correlation provides compelling evidence that a significant portion of the differential gene profiles between GVHD+ and GVHD– donors is imprinted at the hematopoietic stem cell level. Moreover, stability of the gene expression profiles over a one-year period suggests that the profiles result from inherited genetic traits as opposed to environmental factors. The gene with the best GVHD-predictive accuracy was SMAD3, a key component of the TGF-β pathway. By testing a cohort of 450 subjects using qRT-PCR, we found that amounts of SMAD3 transcripts varied over a 6-fold range. In mice and humans, SMAD3 is constitutively activated (as evidenced by phosphorylation and accumulation in the nucleus) in many leukocyte subsets. We found in mice that induction of TGF-β signaling in donor T cells is an early event following AHCT and that Smad3-deficient donors trigger more severe GVHD than wild-type littermates. These findings strongly suggest that the donor gene expression profile has a dominant influence on the occurrence of GVHD. In allogeneic HCT, the ability to discriminate strong and weak alloresponders using gene expression profiling could help select low-risk donors and permit tailoring GVHD prophylaxis regimens according to the probability of GVHD occurrence.

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Single Insulin-Specific CD8+ T Cells Show Characteristic Gene Expression Profiles in Human Type 1 Diabetes

Diabetes ◽

10.2337/db11-0270 ◽

2011 ◽

Vol 60 (12) ◽

pp. 3289-3299 ◽

Cited By ~ 25

Author(s):

S. Luce ◽

F. Lemonnier ◽

J.-P. Briand ◽

J. Coste ◽

N. Lahlou ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Type 1 Diabetes ◽

Cd8 T Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Human Type ◽

Human Type 1 Diabetes

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Faculty Opinions recommendation of Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717980795.793471790 ◽

2013 ◽

Author(s):

Paul Goepfert ◽

Anju Bansal

Keyword(s):

Gene Expression ◽

T Cells ◽

Cd4 T Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Distinct Gene ◽

Hiv 1

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

Journal of Personalized Medicine ◽

10.3390/jpm11121291 ◽

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.

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Phenotypic and clonal stability of antigen-inexperienced memory-like T cells across the genetic background, hygienic status, and aging

10.1101/2020.09.01.277004 ◽

2020 ◽

Author(s):

Alena Moudra ◽

Veronika Niederlova ◽

Jiri Novotny ◽

Lucie Schmiedova ◽

Jan Kubovciak ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Genetic Background ◽

Expression Profiles ◽

Bacterial Colonization ◽

Gene Expression Profiles ◽

Inbred Strains ◽

Microbial Colonization ◽

Independent Manner ◽

Different Genetic Background

AbstractAntigen-inexperienced memory-like T (AIMT) cells are functionally unique T cells representing one of the two largest subsets of murine CD8+ T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multi-omics approaches including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice independently of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122LOW AIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122HIGH AIMT cells (virtual memory) dominate in aged mice. Co-housing with feral mice changed the bacterial colonization of laboratory strains, but had only minimal effects on the CD8+ T-cell compartment including AIMT cells.

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Identification and Validation of a Predictive Immune-related Genes Signature for the Prognosis of Cholangiocarcinoma

10.21203/rs.3.rs-59448/v1 ◽

2020 ◽

Author(s):

Rui Zhang ◽

Chen Chen ◽

Qi Li ◽

Jialu Fu ◽

Dong Zhang ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

High Risk ◽

Risk Score ◽

Risk Model ◽

Predictive Accuracy ◽

Expression Profiles ◽

Gene Expression Profiles ◽

The Cancer Genome Atlas ◽

Immune Related Genes

Abstract Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were signiﬁcantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.

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