scholarly journals Glutamine metabolism regulates Th2 cell differentiation via the α-ketoglutalate-dependent demethylation of histone H3K27

2017 ◽  
Author(s):  
Makoto Kuwahara ◽  
Maya Izumoto ◽  
Hiroaki Honda ◽  
Kazuki Inoue ◽  
Yuuki Imai ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Gene Locus ◽  
Glutamine Metabolism ◽  
T Cell Subsets ◽  
Cytokine Gene ◽  
Th2 Cytokine ◽  
Th2 Cell ◽  
Histone H3k27 ◽  
The Impact

AbstractThe acquisition of T cell functions seems to be closely linked to the reprogramming of the metabolic pathway. However, the impact of metabolic changes on the differentiation of helper T cell subsets remains unclear. We found that TCR-mediated activation of glutamine metabolism regulates Th2 cell differentiation via the supplementation of α-ketogulutalate (α-KG) and histone H3K27 demethylation. Deprivation of glutamine or pharmacological inhibition of glutamine metabolism blocks the induction of Th2 cell differentiation without affecting Stat6 phosphorylation. The methylation status of H3K27 at the Th2 cytokine gene locus was significantly increased in Th2 cells cultured under glutamine-deprived conditions. The inhibitory effect of glutamine-deprivation was antagonized by α-KG, and the α-KG-dependent induction of Th2 cell differentiation was reduced in utx- and jmjd3-deficient naïve CD4 T cells. These findings show that the glutamine-a-ketoglutarate axis is crucial to regulating the epigenetic status at the Th2 cytokine gene locus and subsequent Th2 cell differentiation.

scholarly journals Comparison of selected CD45+ cell subsets’ response and cytokine levels on exhaustive effort among soccer players

2019 ◽  
Vol 38 (3) ◽  
pp. 256-267 ◽  
Author(s):  
Dorota Kostrzewa-Nowak ◽  
Rafał Buryta ◽  
Robert Nowak
Keyword(s):  
T Cell ◽  
Biological Response ◽  
T Cell Subsets ◽  
Alternative Mechanism ◽  
Post Exercise ◽  
Memory T Cell ◽  
Cell Percentage ◽  
Significant Release ◽  
Efficiency Test ◽  
The Impact

SummaryBackgroundImmunological alterations may led to the reduction in capacity and endurance levels in elite athletes by e.g. increased susceptibility to infections. There is a need to explain the impact of intensive physical effort on the CD4+memory T cell subsets.MethodsFourteen participants median aged 19 years old (range 17–21 years) were recruited form Pogoń Szczecin S.A., soccer club. They performed progressive efficiency test on mechanical treadmill until exhaustion twice: during preparatory phases to spring and autumn competition rounds. We examined the influence of exhaustive effort on the selected CD45+, especially CD4+memory T cell subsets and inflammation markers determined before, just after the test and during recovery time.ResultsSignificant changes in total CD45+cells and decrease in T lymphocytes percentage after the run was observed. Significant fluctuations in T cells’ distribution were related not only to the changes in Th or Tc subsets but also to increase in naïve T cell percentage during recovery. Increase in TNF-α and IL-8 post-exercise, IL-6 and IL-10 plasma levels in recovery was also found.ConclusionsThe novel finding of our study is that the run performed on mechanical treadmill caused a significant release of CD4+T naïve cells into circulation. Post-exercise increase in circulating NK cells is related with fast biological response to maximal effort. However, at the same time an alternative mechanism enhancing inflammation is involved.

scholarly journals Robust, But Transient Expression of Adeno-Associated Virus-Transduced Genes During Human T Lymphopoiesis

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4854-4864 ◽  
Author(s):  
Jason P. Gardner ◽  
Haihong Zhu ◽  
Peter C. Colosi ◽  
Gary J. Kurtzman ◽  
David T. Scadden
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Gene Transfer ◽  
Transgene Expression ◽  
Marker Gene ◽  
T Cell Differentiation ◽  
Target Cells ◽  
Hematopoietic Stem ◽  
The Impact ◽  
T Lymphopoiesis

Abstract Recombinant adeno-associated viruses (rAAV) have been proposed to be gene transfer vehicles for hematopoietic stem cells with advantages over other virus-based systems due to their high titers and relative lack of dependence on cell cycle for target cell integration. We evaluated rAAV vector containing a LacZ reporter gene under the control of a cytomegalovirus (CMV) promoter in the context of primary human CD34+CD2− progenitor cells induced to undergo T-cell differentiation using an in vitro T-lymphopoiesis system. Target cells from either adult bone marrow or umbilical cord blood were efficiently transduced, and 71% to 79% CD2+ cells expressed a LacZ marker gene mRNA and produced LacZ-encoded protein after exposure to rAAV-CMV-LacZ. The impact of transgene expression on the differentiation of T cells was assessed by sequential quantitation of immunophenotypic subsets of virus-exposed cells and no alteration was noted compared with control. The durability of transgene expression was assessed and found to decay by day 35 with kinetics dependent on the multiplicity of infection. In addition, vector DNA was absent from CD4 or CD8 subselected CD3+ cells by DNA-polymerase chain reaction. These data suggest that rAAV vectors may result in robust transgene expression in primitive cells undergoing T-cell lineage commitment without toxicity or alteration in the pattern of T-cell differentiation. However, expression is transient and integration of the transgene unlikely. Recombinant AAV vectors are potentially valuable gene transfer tools for the genetic manipulation of events during T-cell ontogony but their potential in gene therapy strategies for diseases such as acquired immunodeficiency syndrome is limited.

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4550-4556 ◽  
Author(s):  
Frederique Ponchel ◽  
Ann W. Morgan ◽  
Sarah J. Bingham ◽  
Mark Quinn ◽  
Maya Buch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Large Population ◽  
Chronic Inflammatory Disease ◽  
T Cell Differentiation ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

scholarly journals O05.2 Characterizing the impact of penile-vaginal sex on HIV-susceptible CD4+ T cell subsets in the female genital tract

2019 ◽  
Author(s):  
Avid Mohammadi ◽  
Sareh Bagherichimeh ◽  
Azadeh Fazel ◽  
Elizabeth Tevlin ◽  
Wangari Tharao ◽  
...  
Keyword(s):  
T Cell ◽  
Genital Tract ◽  
Female Genital Tract ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Vaginal Sex ◽  
The Impact ◽  
Female Genital

Recurrent Respiratory Papillomatosis: Altered CD8+ T-Cell Subsets and TH1/TH2 Cytokine Imbalance

1999 ◽  
Vol 93 (3) ◽  
pp. 302-311 ◽  
Author(s):  
Vincent R. Bonagura ◽  
Lynda Hatam ◽  
James DeVoti ◽  
Feifei Zeng ◽  
Bettie M. Steinberg
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Recurrent Respiratory Papillomatosis ◽  
T Cell Subsets ◽  
Th2 Cytokine ◽  
Cytokine Imbalance

The who's who of T-cell differentiation: Human memory T-cell subsets

2013 ◽  
Vol 43 (11) ◽  
pp. 2797-2809 ◽  
Author(s):  
Yolanda D. Mahnke ◽  
Tess M. Brodie ◽  
Federica Sallusto ◽  
Mario Roederer ◽  
Enrico Lugli
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Human Memory ◽  
T Cell Differentiation ◽  
T Cell Subsets ◽  
Memory T Cell

In Vivo Cytokine Gene Expression in Various T Cell Subsets of the Autoimmune MRL/Mp-lpr/lpr Mouse

Autoimmunity ◽  
1994 ◽  
Vol 17 (1) ◽  
pp. 49-57 ◽  
Author(s):  
K. Mori ◽  
S. Kobayashi ◽  
M. Inobe ◽  
W. Y. Jia ◽  
M. Tamakosh ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Subsets ◽  
Cytokine Gene Expression ◽  
Cytokine Gene
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