scholarly journals Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of naïve T lymphocytes

2011 ◽  
Vol 8 (1) ◽  
Author(s):  
Michiyo Ohyashiki ◽  
Junko H Ohyashiki ◽  
Ayako Hirota ◽  
Chiaki Kobayashi ◽  
Kazuma Ohyashiki
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Age Related ◽  
Naive T Lymphocytes

scholarly journals CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

2004 ◽  
Vol 200 (11) ◽  
pp. 1407-1417 ◽  
Author(s):  
Adrian F. Ochsenbein ◽  
Stanley R. Riddell ◽  
Michele Brown ◽  
Lawrence Corey ◽  
Gabriela M. Baerlocher ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Effector Memory ◽  
Term Survival ◽  
Functional Consequences

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response.

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

Immunosenescence of Lymphocytes T and Implications for Age-Related Disorders

2020 ◽  
Author(s):  
Anna Tylutka ◽  
Barbara Morawin ◽  
Artur Gramacki ◽  
Agnieszka Zembron-Lacny
Keyword(s):  
T Cells ◽  
Elderly People ◽  
Cd8 T Cells ◽  
The Elderly ◽  
Health Concern ◽  
Female Group ◽  
Major Health ◽  
Cd8 Cells ◽  
Age Related ◽  
Sex Disorders

Abstract Background. The decrease in immunity with age is still a major health concern as elderly people are more susceptible to infections and increased incidence of autoimmunity. Consequently, there is an increasing interest in immunosenescence and changes in immunology cells like T cells. The aim of our study was to find a disproportion in subpopulation of T cells as well as CD4/CD8 ratio depending on the age, gender or comorbidities. Results. In the present study, a flow cytometry was used to indicate the differences between age, sex, disorders and fat content in the CD4+ and CD8+ T cells population divided into naïve and memory cells as well as CD4/CD8 ratio in people aged 71.9± 5.8 years (females n=83, males n=16) compared to young people aged 20.6 ± 1.1 years (females n=12, males n=19). The percentage of naïve CD4+ and CD8+ cells was found to be statistically significantly lower in the elderly compared to the young. In addition, gender was observed to play an important role in the outcomes in the analysed subpopulations and in female group, who live statistically longer than males, our older group of Polish women demonstrated a significantly higher percentage of naïve lymphocytes in both the CD4+ and CD8+ populations compared to men. The CD4/CD8 ratio increases with age, which can be considered one of the markers determining longevity. Elderly people with age-related diseases (hypertension) also show an increased level of CD4/CD8 ratio as well as CD4+. Conclusion. We demonstrated that changes in the T cells population, including naïve cell population as well as CD4/CD8 ratio, are important markers which can be predictive of healthy status. In order to accurately determine longevity, gender or age-associated diseases should be taken into account.

scholarly journals Phenotypic and clonal analysis of T lymphocytes in childhood immune thrombocytopenic purpura

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2137-2142 ◽  
Author(s):  
RE Ware ◽  
TA Howard
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Immune Thrombocytopenic Purpura ◽  
Clonal Analysis ◽  
In Vitro Proliferation ◽  
Cell Reactivity ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Age Related

Abstract In an attempt to identify and characterize T-lymphocyte immunoregulatory abnormalities in immune thrombocytopenic purpura (ITP), we have performed phenotypic and clonal analysis on peripheral T lymphocytes from 23 children with ITP. Quantitation of lymphocyte subpopulations showed that children with acute ITP had higher numbers of CD45RA+ and lower numbers of CD45RO+ T cells than children with chronic ITP or controls, but these differences may be age related. Analysis of T-cell receptor variable beta gene usage identified 2 boys with chronic ITP and elevated numbers of V beta 8+ T cells. Eight T- cell clones were established (6 CD4+, 4B4+ helper-inducer lines and 2 CD8+ lines) that showed in vitro proliferation against allogeneic platelets. The addition of autologous antigen-presenting cells enhanced the proliferation of six clones, but not for two clones that coexpressed natural killer (NK) markers. Four of seven positive clones also had measurable interleukin (IL)-2 secretion following platelet stimulation, providing further evidence for T-cell reactivity. Our results provide the first evidence that patients with ITP may have platelet-reactive T lymphocytes identifiable at the clonal level, supporting the hypothesis that autoreactive peripheral T lymphocytes may mediate or participate in the pathogenesis of this disorder.

IL-21 Gene Modified T Antigen Presenting Cells Enhance the Generation of Tumor-Specific Cytotoxic T Lymphocytes with a Memory Phenotype.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3709-3709
Author(s):  
Anjum S. Kaka ◽  
Ryan Hartmeier ◽  
Ann M. Leen ◽  
An Lu ◽  
Cliona M. Rooney ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Cultures ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Antigen Presenting Cells ◽  
Memory Phenotype ◽  
Cytotoxicity Assays ◽  
Antigen Presenting

Abstract IL-21 is a potent cytokine that augments the proliferation and effector function of NK cells and acts in synergy with other γ-chain cytokines to enhance the cytotoxicity of T lymphocytes. IL-21 is transiently produced by activated CD4+ T cells and may facilitate the generation of effector and memory T cells. Recently, T cells have been shown to be effective antigen presenting cells (TAPC) and we hypothesized that this characteristic may be enhanced through overexpression of IL-21 following genetic modification of TAPC. We demonstrate here that transduction of TAPC with IL-21 significantly enhances the generation of MART-1-specific CD8+ T cells suggesting a potential use for IL-21 in tumor immunotherapy protocols. IL-21 was cloned from CD3/CD28-activated CD4+ T cells and inserted into the SFG retroviral vector. To generate IL-21-producing T-APC, CD8-selected T cells from healthy, HLA-A2 donors were stimulated on αCD3/αCD28-coated plates in the presence of IL-2. After 2 days, activated cells were harvested and transduced on Retronectin-coated plates with IL-21 retroviral supernatant. On day 5, TAPC were washed and expanded in growth media supplemented by IL-2. Prior to use as APCs, TAPCs were CD4-depleted by MACS to eliminate residual IL-21 production by CD4+ T cells. IL-21-transduced and non-transduced (NT) CD8+ TAPC pulsed with MART-1 HLA-A2-restricted peptide (ELAGIGILTV) were irradiated and cocultured with autologous CD8+ peripheral blood T cells in media supplemented with IL-7 and IL-12. On day 7, responder T cell cultures were restimulated with peptide-loaded IL-21 or NT CD8+ TAPCs in the presence of IL-2 to induce expansion. Responder T cell cultures were then analyzed for MART-1 specificity by pentamer, ELISPOT and cytotoxicity assays and for their memory phenotype using monoclonal antibodies to CD27, CD28, CD62L, CD45RA, CD45RO, CD127 and CCR7. TAPC were efficiently expanded (>100-fold expansion) and transduced by retrovirus encoding IL-21 (>50% as measured by GFP). Gene modification of TAPC with IL-21 had minimal effect on MHC class I, II, CD80, CD83 and CD86 levels when compared to NT TAPC. However, there was increased expression of CD27, CD28 and CD62L, suggesting that IL-21 was biologically active. Seven days after stimulation with MART-1/ELA peptide-pulsed IL-21-TAPC and NT-TAPC, we observed a substantial increase (10±5-fold) in ELA-specific T cells in cultures stimulated with IL-21-TAPC compared to NT-TAPC when analyzed by FACS using ELA pentamers. Subsequent stimulation with IL-21-TAPCs amplified this effect, resulting in >50-fold increase in absolute ELA-specific T cell numbers when compared to NT-TAPC. ELA-specific CTL generated from IL-21-TAPC stimulation were functional as determined by IFN-γ ELISPOT and cytotoxicity assays. ELA-specific CTL generated from IL-21-TAPC exhibited a unique phenotype (CD45RA−, CD27high, CD28high, CD62Lhigh) as compared to CTL generated form NT-TAPC (CD45RA−, CD27low, CD28low, CD62Llow) suggesting that IL-21 may play a role in the development of T cell memory. In summary, IL-21 enhances the generation of tumor-specific CD8+ T cells which exhibit a central/effector memory phenotype. Our results indicate that IL-21 improves proliferation of antigen-specific T cells, possibly by maintaining CD28 expression allowing costimulation upon secondary antigen encounter.

In Vitro Generation of Cytotoxic T Lymphocytes against MAGE A1 and MAGE A3 Derived From Healthy Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4079-4079
Author(s):  
Lei Bao ◽  
Mindy M Stamer ◽  
Kimberly Dunham ◽  
Deepa Kolaseri Krishnadas ◽  
Kenneth G Lucas
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Target Cells ◽  
Ifn Gamma ◽  
Healthy Donors

Abstract Abstract 4079 Poster Board III-1014 MAGE A1 and MAGE A3 are cancer testis antigens that are expressed on a number of malignant tumor cells, but not by normal cells, except for male germ cells which lack HLA expression. Therefore, MAGE cytotoxic T lymphocytes are strictly tumor-specific. Adoptive transfer of antigen specific cytotoxic T lymphocytes (CTL) provides immediate graft-versus tumor effects while minimizing risk for graft-versus-host disease. The aim of the current study was to find ideal conditions for expansion of CTL targeting tumor-associated antigens from peripheral blood mononuclear cells (PBMCs) of healthy donors to be used in allogenic cell therapy. In this study we investigated the ability to generate MAGE A1 and MAGE A3 specific cytotoxic T cells using autologous dendritic cells (DC) loaded with MAGE A1 and MAGE A3 overlapping peptides. CTL lines specific for MAGE A1 and MAGE A3 were established by stimulating CD8 T cells from healthy donors with autologous dendritic cells loaded with MAGE A1 or MAGE A3 overlapping pooled peptides in round-bottomed, 96-well plates. CD8+ T cells were restimulated with the same ratio of peptide pulsed DC on days 7 and 14 in the presence of IL-2 (50 U/ml), IL-7 and IL-15 (5 ng/ml). These microcultures were screened 10 days after the third stimulation for their capacity to produce interferon-gamma (IFN-gamma) when stimulated with autologous EBV-transformed B lymphocytes (BLCL) transduced with lentivirus(LV) encoding MAGE A1 or MAGE A3 and autologous BLCL transduced with LV encoding GFP. MAGE A1 and MAGE-A3 specific IFN-gamma producing cells were rapidly expanded in OKT3 and IL2. The specificity of the rapidly expanded MAGE A1 and MAGE A3 specific T cells was confirmed by IFN-gamma production as measured by intracellular cytokine staining and ELISA as well as antigen specific cytotoxicity by a standard 51chromium (51Cr) release assay. We successfully generated MAGE A1 and MAGE A3 specific CTL lines from healthy donors using this method. Specific CTL lines showed cytotoxicity in vitro not only to target cells pulsed with MAGE A1 or MAGE A3 peptides but also to target cells transduced with LV-MAGE A1 or LV-MAGE A3. Specific cytolytic activity was accompanied by IFN-gamma secretion. These data indicate that tumor antigen specific CTL can be expanded using overlapping peptides regardless of an individual's HLA specificity. The ability to generate tumor specific CTL from donors of various HLA backgrounds provide a rationale for utilizing MAGE A1 and MAGE A3 overlapping peptides for expansion of antigen specific T cells for adoptive T-cell therapy against MAGE A1 or MAGE A3 expressing tumors. Disclosures: No relevant conflicts of interest to declare.

Association between gut microbiome and T lymphocytes among different primary tumor sites of patients with metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16013-e16013
Author(s):  
Lingyun Sun ◽  
Yunzi Yan ◽  
Dongmei Chen ◽  
Jun J. Mao ◽  
Yufei Yang
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Primary Tumor ◽  
Principal Component ◽  
Alpha Diversity ◽  
T Lymphocyte Subsets ◽  
Cell Immunity ◽  
Xiyuan Hospital

e16013 Background: Different primary tumor sites could impact colorectal cancer (CRC)’s survival outcomes and treatment effects. Previous studies had found that gut micro-biome distributions were different between left and right colon cancer(LCC, RCC). Out study aimed to further investigate the association between micro-biome and T lymphocytes among different tumor sites of patients with metastatic CRC. Methods: Between April 2018 and Mars 2019, we enrolled 40 metastatic CRC patients in Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China. We collected patients’ stool samples for micro-biome analysis by 16s rRNA sequencing approaches, as well as patients’ blood samples to analyses T lymphocyte subsets by flow cytometry methods. The study had been proved by ethics committee of Xiyuan Hospital (2016XLA122-1). All patients consented before enrollment. Results: Among 40 patients, 28% were female, with average age of 63±15 years old. There were 10 RCC, 9 LCC and 21 rectal cancer(RC) patients. Alpha diversity analysis showed that sobs index of the micro-biome of patients with RC and RC was significantly higher than whom were RCC(254.89±99, 247±89 versus.[vs.]101.17±51, p= 0.001). PCoA analysis on OTU level detected that first principal component[PC1] (26.24%) could be separated significantly between RCC and LCC( p= 0.048), as well as between RC and RCC (PC1,14.17%, p= 0.024). Community analysis showed that the proportion of Bacteroidetes was significantly higher in patients with RCC than whom with LCC and RC( p= 0.009). Conversely, the proportion of Firmicutes, Proteobacteria and Verrucomicrobia were higher in LCC patients than others( p= 0.37, 0.047 and 0.032 respectively). Canonical Correlation Analysis (CCA) analysis proved that the CD4+ and CD8+ T cells counts were environmental factors, which were significantly associated with certain micro-biome and samples from different tumor sites( p= 0.037 and 0.01 respectively). Trends showed that CD4+ T cells were positively related with samples of RC and bacteria parabacteroides and bifidobacterium, while CD8+ T cells were positively related with samples of RCC and bacteria Lachnospira, Sutterella and Bacteroides. Conclusions: In our study, we found that patients with LCC and RC had more beneficial gut micro-biome than whom with RCC. In addition, such difference might be associated with body T cell immunity.

scholarly journals Alterations in T-Cell Receptor Vβ Repertoire of CD4 and CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Children

2003 ◽  
Vol 10 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Monica Kharbanda ◽  
Thomas W. McCloskey ◽  
Rajendra Pahwa ◽  
Mei Sun ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Chronic Phase ◽  
Cell Receptor ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus

ABSTRACT Perturbations in the T-cell receptor (TCR) Vβ repertoire were assessed in the CD4 and CD8 T lymphocytes of human immunodeficiency virus (HIV)-infected children who were receiving therapy during the chronic phase of infection by flow cytometry (FC) and PCR analysis. By FC, representation of 21 TCR Vβ subfamilies was assessed for an increased or decreased percentage in CD4 and CD8 T cells, and by PCR, 22 TCR Vβ subfamilies of CD4 and CD8 T cells were analyzed by CDR3 spectratyping for perturbations and reduction in the number of peaks, loss of Gaussian distribution, or clonal dominance. The majority of the TCR Vβ subfamilies were examined by both methods and assessed for deviation from the norm by comparison with cord blood samples. The CD8-T-lymphocyte population exhibited more perturbations than the CD4 subset, and clonal dominance was present exclusively in CD8 T cells. Of the 55 total CD8-TCR Vβ families classified with clonal dominance by CDR3 spectratyping, only 18 of these exhibited increased expression by FC. Patients with high numbers of CD8-TCR Vβ families with decreased percentages had reduced percentages of total CD4 T cells. Increases in the number of CD4-TCR Vβ families with increased percentages showed a positive correlation with skewing. Overall, changes from normal were often discordant between the two methods. This study suggests that the assessment of HIV-induced alterations in TCR Vβ families at cellular and molecular levels yields different information and that our understanding of the immune response to HIV is still evolving.

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