scholarly journals Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b

2010 ◽  
Vol 207 (8) ◽  
pp. 1687-1699 ◽  
Author(s):  
Shuning Zhang ◽  
Mike Rozell ◽  
Raj K. Verma ◽  
Diana I. Albu ◽  
Danielle Califano ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Cytolytic Activity ◽  
Tcr Signaling ◽  
Expansion Phase ◽  
Cd8 T Lymphocytes ◽  
Cell Immunity

CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course of infection in the absence of Bcl11b, albeit in smaller numbers, and their Ag-specific cytolytic activity on a per-cell basis was altered, which was associated with reduced granzyme B and perforin.

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.

scholarly journals Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1474-1479 ◽  
Author(s):  
Marcelo J. Kuroda ◽  
Jörn E. Schmitz ◽  
Aruna Seth ◽  
Ronald S. Veazey ◽  
Christine E. Nickerson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymph Node ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Rhesus Monkeys ◽  
Cd8 T Lymphocytes ◽  
Tetramer Binding ◽  
Immunodeficiency Virus

Major histocompatibility class I–peptide tetramer technology and simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys were used to clarify the distribution of acquired immunodeficiency syndrome virus-specific cytotoxic T lymphocytes (CTL) in secondary lymphoid organs and to assess the relationship between these CTL and the extent of viral replication in the various anatomic compartments. SIVmac Gag epitope-specific CD8+ T cells were evaluated in the spleen, bone marrow, tonsils, thymus, and 5 different lymph node compartments of 4 SIVmac-infected rhesus monkeys. The average percentage of CD8+ T lymphocytes that bound this tetramer in all the different lymph node compartments was similar to that in peripheral blood lymphocytes in individual monkeys. The percentage of CD8+ T cells that bound the tetramer in the thymus was uniformly low in the monkeys. However, the percentage of CD8+ T cells that bound the tetramer in bone marrow and spleen was consistently higher than that seen in lymph nodes and peripheral blood. The phenotypic profile of the tetramer-binding CD8+ T lymphocytes in the different lymphoid compartments was similar, showing a high expression of activation-associated adhesion molecules and a low level expression of naive T-cell–associated molecules. Surprisingly, no correlation was evident between the percentage of tetramer-binding CD8+ T lymphocytes and the magnitude of the cell-associated SIV RNA level in each lymphoid compartment of individual monkeys. These studies suggest that a dynamic process of trafficking may obscure the tendency of CTL to localize in particular regional lymph nodes or that some lymphoid organs may provide milieus that are particularly conducive to CTL expansion.

scholarly journals Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1474-1479 ◽  
Author(s):  
Marcelo J. Kuroda ◽  
Jörn E. Schmitz ◽  
Aruna Seth ◽  
Ronald S. Veazey ◽  
Christine E. Nickerson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymph Node ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Rhesus Monkeys ◽  
Cd8 T Lymphocytes ◽  
Tetramer Binding ◽  
Immunodeficiency Virus

Abstract Major histocompatibility class I–peptide tetramer technology and simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys were used to clarify the distribution of acquired immunodeficiency syndrome virus-specific cytotoxic T lymphocytes (CTL) in secondary lymphoid organs and to assess the relationship between these CTL and the extent of viral replication in the various anatomic compartments. SIVmac Gag epitope-specific CD8+ T cells were evaluated in the spleen, bone marrow, tonsils, thymus, and 5 different lymph node compartments of 4 SIVmac-infected rhesus monkeys. The average percentage of CD8+ T lymphocytes that bound this tetramer in all the different lymph node compartments was similar to that in peripheral blood lymphocytes in individual monkeys. The percentage of CD8+ T cells that bound the tetramer in the thymus was uniformly low in the monkeys. However, the percentage of CD8+ T cells that bound the tetramer in bone marrow and spleen was consistently higher than that seen in lymph nodes and peripheral blood. The phenotypic profile of the tetramer-binding CD8+ T lymphocytes in the different lymphoid compartments was similar, showing a high expression of activation-associated adhesion molecules and a low level expression of naive T-cell–associated molecules. Surprisingly, no correlation was evident between the percentage of tetramer-binding CD8+ T lymphocytes and the magnitude of the cell-associated SIV RNA level in each lymphoid compartment of individual monkeys. These studies suggest that a dynamic process of trafficking may obscure the tendency of CTL to localize in particular regional lymph nodes or that some lymphoid organs may provide milieus that are particularly conducive to CTL expansion.

scholarly journals Lineage-specific Requirement for Signal Transducer and Activator of  Transcription (Stat)4 in Interferon γ Production from CD4+ Versus CD8+ T Cells

1999 ◽  
Vol 189 (8) ◽  
pp. 1355-1360 ◽  
Author(s):  
Laura L. Carter ◽  
Kenneth M. Murphy
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Cytolytic Activity ◽  
Signal Transducer ◽  
Specific Requirement ◽  
Tcr Signaling ◽  
Effector Functions ◽  
Ifn Γ

CD4+ and CD8+ T cells exhibit important differences in their major effector functions. CD8+ T cells provide protection against pathogens through cytolytic activity, whereas CD4+ T cells exert important regulatory activity through production of cytokines. However, both lineages can produce interferon (IFN)-γ, which can contribute to protective immunity. Here we show that CD4+ and CD8+ T cells differ in their regulation of IFN-γ production. Both lineages require signal transducer and activator of transcription (Stat)4 activation for IFN-γ induced by interleukin (IL)-12/IL-18 signaling, but only CD4+ T cells require Stat4 for IFN-γ induction via the TCR pathway. In response to antigen, CD8+ T cells can produce IFN-γ independently of IL-12, whereas CD4+ T cells require IL-12 and Stat4 activation. Thus, there is a lineage-specific requirement for Stat4 activation in antigen-induced IFN-γ production based on differences in TCR signaling between CD4+ and CD8+ T cells.

scholarly journals B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo

2001 ◽  
Vol 194 (9) ◽  
pp. 1339-1348 ◽  
Author(s):  
Xingluo Liu ◽  
Xue-Feng Bai ◽  
Jing Wen ◽  
Jian-Xin Gao ◽  
Jinqing Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Tumor Antigen ◽  
Costimulatory Molecule ◽  
Clonal Expansion ◽  
Immune Protection ◽  
Large Tumor ◽  
Cd8 T Lymphocytes

B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H+ tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7–1 and B7–2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H+ and B7H− tumors were coinjected, P1CTL selectively eliminated the B7H+ tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2Ld, the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8+ T lymphocytes in vivo.

scholarly journals Epigenetic Control of Interferon-Gamma Expression in CD8 T Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Patrícia S. de Araújo-Souza ◽  
Steffi C. H. Hanschke ◽  
João P. B. Viola
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Cd8 T Lymphocytes ◽  
Conserved Noncoding Sequences ◽  
Differential Gene ◽  
Posttranslational Histone Modifications ◽  
Th 1

Interferon- (IFN-)γis an essential cytokine for immunity against intracellular pathogens and cancer. IFN-γexpression by CD4 T lymphocytes is observed only after T helper (Th) 1 differentiation and there are several studies about the molecular mechanisms that control Ifng expression in these cells. However, naïve CD8 T lymphocytes do not produce large amounts of IFN-γ, but after TCR stimulation there is a progressive acquisition of IFN-γexpression during differentiation into cytotoxic T lymphocytes (CTL) and memory cells, which are capable of producing high levels of this cytokine. Differential gene expression can be regulated from the selective action of transcriptional factors and also from epigenetic mechanisms, such as DNA CpG methylation or posttranslational histone modifications. Recently it has been recognized that epigenetic modification is an integral part of CD8 lymphocyte differentiation. This review will focus on the chromatin status of Ifng promoter in CD8 T cells and possible influences of epigenetic modifications in Ifng gene and conserved noncoding sequences (CNSs) in regulation of IFN-γproduction by CD8 T lymphocytes.

scholarly journals Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study

2020 ◽  
Vol 41 (37) ◽  
pp. 3549-3560 ◽  
Author(s):  
David M Leistner ◽  
Nicolle Kränkel ◽  
Denitsa Meteva ◽  
Youssef S Abdelwahed ◽  
Claudio Seppelt ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Coronary Syndrome ◽  
T Cell ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Coronary Plaque ◽  
Effector Molecules ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Cd8 T Lymphocytes

Abstract Aims  Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. Methods and results  The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. Conclusions  The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. Trial registration The study was registered at clinicalTrials.gov (NCT03129503).

scholarly journals MODULATORY EFFECT OF PROBIOTIC THERAPY ON INTESTINAL LYMPHOCYTES IN MICE INFECTED WITH TRICHINELLA SPIRALIS

2019 ◽  
pp. 741-745
Author(s):  
Emília Dvorožňáková ◽  
Miroslava Vargová ◽  
Andrea Lauková ◽  
Viera Revajová
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
B Cells ◽  
T Lymphocytes ◽  
Lamina Propria ◽  
Cd8 T Cells ◽  
Trichinella Spiralis ◽  
Parasitic Infection ◽  
Bacterial Strains ◽  
Cd8 T Lymphocytes

Important components of the intestinal mucosal immunity are free intraepithelial and lamina propria lymphocytes involved in the regulation and activity of the immune response. This study detected the presence of helper CD4 and cytotoxic CD8 T lymphocytes, and B lymphocytes in the small intestine of mice treated with probiotic strains and infected with Trichinella spiralis. Bacterial strains of different origin (Enterococcus faecium CCM8558, Enterococcus durans ED26E/7, Lactobacillus fermentum CCM7421, Lactobacillus plantarum 17L/1) were administered daily in dose of 109CFU/ml in 100 μl and mice were infected with 400 larvae of T. spiralison 7th day of treatment. L. fermentum CCM7421 and L. plantarum 17L/1 increased numbers of helper CD4 T cells in the epithelium and cytotoxic CD8 T cells in the lamina propria on 7th day of administration (before parasitic infection). T. spiralisinfection caused a significant inhibition of examined lymphocyte subpopulations from 5 to 25 days post infection (p.i.). Lactobacilli restored the CD4 T cell numbers in the epithelium and lamina propria on the level of healthy control from day 11 p.i. All strains stimulated the numbers of CD8 T cells in infected mice, but in comparison to control, CD8 T cells were reduced in the epithelium until day 25 p.i. and in the lamina propria only on day 5 p.i. An inhibition of B cells (CD19) in the small intestine after T. spiralis infection was not affected by probiotic therapy till day 25 p.i., but a stimulation of B cells was found after treatment with E. durans ED26E/7 and L. fermentum CCM7421on day 32 p.i. The obtained results confirmed the strain-specific immunomodulatory effect of probiotic bacteria. The greatest immunomodulatory potential on the gut CD4 and CD8 T lymphocytes during T. spiralis infection was confirmed by L. fermentum CCM7421 and L. plantarum 17L/1. Strains E. faecium CCM8558 and E. durans ED26E/7 activated only cytotoxic CD8 T cells in the lamina propria.

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