scholarly journals The Effect of Lipid Metabolism on CD4+ T Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Feiyang Cai ◽  
Shuxin Jin ◽  
Guangjie Chen
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Adaptive Immune System ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Immune Disorder

CD4+ T cells play a vital role in the adaptive immune system and are involved in the pathogenesis of many diseases, including cancer, autoimmune diseases, and chronic inflammation. As an important mechanism for energy storage, a lot of researches have clarified that metabolism imbalance interacts with immune disorder, and one leads to the other. Lipid metabolism has close relationship with CD4+ T cells. In this review, we discuss fatty acid, cholesterol, prostaglandin, and phospholipid metabolism in CD4+ T cell subsets. Fatty acid β-oxidation (FAO) is activated in Th17 cell to support the proinflammatory function. Cholesterol promotes Th1, Th2, and Treg cell differentiation. In addition to glucose metabolism, lipid metabolism is also very important for immunity. Here, it is highlighted that lipid metabolism regulates CD4+ T cell differentiation and function and is related to diseases.

scholarly journals CD4+ T cell subsets present stable relationships in their T cell receptor repertoires

2020 ◽  
Author(s):  
Shiyu Wang ◽  
Longlong Wang ◽  
Ya Liu
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Antigen Specificity ◽  
Sequence Composition

AbstractCD4+ T cells are key components of adaptive immunity. The cell differentiation equips CD4+ T cells with new functions. However, the effect of cell differentiation on T cell receptor (TCR) repertoire is not investigated. Here, we examined the features of TCR beta (TCRB) repertoire of the top clones within naïve, memory and regular T cell (Treg) subsets: repertoire structure, gene usage, length distribution and sequence composition. First, we found that memory subsets and Treg would be discriminated from naïve by the features of TCRB repertoire. Second, we found that the correlations between the features of memory subsets and naïve were positively related to differentiation levels of memory subsets. Third, we found that public clones presented a reduced proportion and a skewed sequence composition in differentiated subsets. Furthermore, we found that public clones led naïve to recognize a broader spectrum of antigens than other subsets. Our findings suggest that TCRB repertoire of CD4+ T cell subsets is skewed in a differentiation-depended manner. Our findings show that the variations of public clones contribute to these changes. Our findings indicate that the reduce of public clones in differentiation trim the antigen specificity of CD4+ T cells. The study unveils the physiological effect of memory formation and facilitates the selection of proper CD4+ subset for cellular therapy.

Micro-RNA Profiling in CD4+ T Cell Differentiation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3887-3887
Author(s):  
Arnob Banerjee ◽  
Felix Schambach ◽  
Scott Hammond ◽  
Steven Reiner
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
T Cell Differentiation ◽  
Micro Rna ◽  
Cd4 T Cell ◽  
T Helper ◽  
Micro Rnas

Abstract Micro-RNAs comprise a class of small noncoding RNAs which have been found to be important regulators of cellular differentiation in multiple species. Previous analysis of micro-RNA expression in the murine hematopoietic system has suggested a role in cell differentiation and the maintenance of cell identity. Naïve progenitor CD4+ T cells respond to a combination of appropriate antigen and other specific signals by undergoing proliferation and further differentiation into one of at least two subsets. T helper 1 (TH1) cells produce high levels of the cytokine IFN-γ and T helper 2 (TH2) cells produce high levels of IL-4, optimizing them for control of intracellular and extracellular pathogens, respectively. It is currently not known whether micro-RNA molecules influence CD4+ T cell differentiation. We have used oligonucleotide arrays to analyze micro-RNA expression profiles of freshly isolated murine CD4+ T cells compared to cells differentiating into TH1 and TH2 subsets. Expression profiles were found to differ significantly between naïve and stimulated CD4+ cells, with fewer differences between TH1 and TH2 subsets. Promising candidate micro-RNAs are being further evaluated by northern blot and genetic studies. Micro-RNA-155 is upregulated on stimulation of CD4+ T cells in multiple oligonucleotide array assays. Micro-RNA-155 is encoded by the BIC oncogene and has been implicated in lymphomagenesis as well as in other malignancies. We have verified the induction of micro-RNA-155 in stimulated helper T cells by northern blot and are studying the effects of this micro-RNA on CD4+ T cell differentiation. Our observations support a role for micro-RNAs in helper T cell differentiation during the immune response.

A Variety of T-Cell Subsets Contribute to CD4+ T-Cell Infiltration in Diffuse Large B-Cell Lymphoma and Both Total CD4+ and CD4+FoxP3+ T-Cell Numbers Predict Clinical Outcome,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3684-3684
Author(s):  
Matthew J Ahearne ◽  
Kaljit S Bhuller ◽  
Roger Hew ◽  
Giovanna Roncador ◽  
Martin J.S. Dyer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcome ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Good Clinical Outcome ◽  
Logrank Test ◽  
Tfh Cells

Abstract Abstract 3684 CD4+ T-cells can be distinguished into subsets on the basis of surface marker expression and growth factor production. Follicular helper T-cells (Tfh cells) are characterized by the co-expression of surface markers (CD4, ICOS, PD1 and CXCR5) and nuclear BCL6. Normal germinal centre formation requires Tfh cells but is repressed by another CD4+ T-cell subset, Tregs, (demonstrating CD4 and CD25 expression with nuclear FoxP3). The numbers and architecture of infiltrating T-cells predict clinical outcome in follicular lymphoma but although T-cells are a component of diffuse large B cell lymphoma (DLBCL), the relative numbers of CD4+ T-cells and their Tfh and Treg subsets or their association with clinical outcome is not known. We used immunohistochemistry to investigate infiltration by total CD4+, Treg and Tfh cells in cases (n=23) from one centre. The male:female was 1.3:1.0, the age range was 30 to 78 years (median 65 years) and the anticipated association between overall survival and LDH (logrank test, P=0.02) was observed. Patients were treated with R-CHOP with a 21-day cycle. Histological sections were stained with anti-CD4, anti-PD1 and anti-FoxP3 antibodies. For each antibody the area of staining was measured using ImageJ software from 10 high power fields from the same area of each histological section. Tfh cells were identified by strong surface expression of PD1 and Tregs by nuclear expression of FoxP3. CD4+ T-cell infiltration varied by ∼50-fold, and could be diffuse or focal. In 13 cases (57%) the majority of CD4+ T-cells were neither FoxP3+ nor PD1+. Total CD4+ T-cell numbers were positively correlated with FoxP3 (P=0.04) (Figure 1) and with PD1 (P=0.009) (Figure 2) expressing cells suggesting that these subsets were expanded as part of a reaction to the lymphoma capable of stimulating several CD4+ T-cell subsets. High CD4+ (Figure 3) and PD1+ staining predicted good clinical outcome (logrank test, P=0.08) with median survival not being reached at 5 years, but the amount of FoxP3+ staining appeared to be a superior prognostic marker (logrank test, P=0.0069) (Figure 4). There was no association between the cell of origin classification of DLBCL (GCB or ABC) as defined immunohistochemically, and CD4, FoxP3 or PD1 expression. In summary, we have shown that numbers of infiltrating CD4+ T-cells vary between cases of DLBCL and comprises several T-cell subsets including Treg and Tfh cells. No consensus has been reached on the clinical significance of FoxP3+ cell infiltration in DLBCL. Whilst some workers have shown FoxP3 to be associated with a good clinical outcome (Tzankov A., et al. 2008; Lee N., et al. 2008), others have not found a relationship to prognosis (Hasselblom S. et al., 2007). Our data shows that the FoxP3+ Treg cell subset is associated with good clinical outcome but surprisingly we found that both increased total CD4+ T-cells and PD1+ Tfh cells also carry a good prognosis. Disclosures: Wagner: Roche: Honoraria.

scholarly journals Cd4+ T Cell Subsets during Virus Infection

2000 ◽  
Vol 191 (12) ◽  
pp. 2159-2170 ◽  
Author(s):  
Kevin J. Maloy ◽  
Christoph Burkhart ◽  
Tobias M. Junt ◽  
Bernhard Odermatt ◽  
Annette Oxenius ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Delayed Type Hypersensitivity ◽  
Protective Capacity ◽  
Peripheral Tissues

To analyze the antiviral protective capacities of CD4+ T helper (Th) cell subsets, we used transgenic T cells expressing an I-Ab–restricted T cell receptor specific for an epitope of vesicular stomatitis virus glycoprotein (VSV-G). After polarization into Th1 or Th2 effectors and adoptive transfer into T cell–deficient recipients, protective capacities were assessed after infection with different types of viruses expressing the VSV-G. Both Th1 and Th2 CD4+ T cells could transfer protection against systemic VSV infection, by stimulating the production of neutralizing immunoglobulin G antibodies. However, only Th1 CD4+ T cells were able to mediate protection against infection with recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G). Similarly, only Th1 CD4+ T cells were able to rapidly eradicate Vacc-IND-G from peripheral organs, to mediate delayed-type hypersensitivity responses against VSV-G and to protect against lethal intranasal infection with VSV. Protective capacity correlated with the ability of Th1 CD4+ T cells to rapidly migrate to peripheral inflammatory sites in vivo and to respond to inflammatory chemokines that were induced after virus infection of peripheral tissues. Therefore, the antiviral protective capacity of a given CD4+ T cell is governed by the effector cytokines it produces and by its migratory capability.

scholarly journals CD4+ T-Cell Plasticity in Non-Infectious Retinal Inflammatory Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9584
Author(s):  
Yi-Hsing Chen ◽  
Sue Lightman ◽  
Virginia L. Calder
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Dual Function ◽  
Interleukin 17 ◽  
Th1 Cells

Non-infectious uveitis (NIU) is a potentially sight-threatening disease. Effector CD4+ T cells, especially interferon-γ-(IFNγ) producing Th1 cells and interleukin-17-(IL-17) producing Th17 cells, are the major immunopathogenic cells, as demonstrated by adoptive transfer of disease in a model of experimental autoimmune uveitis (EAU). CD4+FoxP3+CD25+ regulatory T cells (Tregs) were known to suppress function of effector CD4+ T cells and contribute to resolution of disease. It has been recently reported that some CD4+ T-cell subsets demonstrate shared phenotypes with another CD4+ T-cell subset, offering the potential for dual function. For example, Th17/Th1 (co-expressing IFNγ and IL-17) cells and Th17/Treg (co-expressing IL-17 and FoxP3) cells have been identified in NIU and EAU. In this review, we have investigated the evidence as to whether these ‘plastic CD4+ T cells’ are functionally active in uveitis. We conclude that Th17/Th1 cells are generated locally, are resistant to the immunosuppressive effects of steroids, and contribute to early development of EAU. Th17/Treg cells produce IL-17, not IL-10, and act similar to Th17 cells. These cells were considered pathogenic in uveitis. Future studies are needed to better clarify their function, and in the future, these cell subsets may in need to be taken into consideration for designing treatment strategies for disease.

scholarly journals Tuberculosis Antigen-Specific T-Cell Responses During the First 6 Months of Antiretroviral Treatment

2019 ◽  
Vol 221 (1) ◽  
pp. 162-167 ◽  
Author(s):  
Catherine Riou ◽  
Nishtha Jhilmeet ◽  
Molebogeng X Rangaka ◽  
Robert J Wilkinson ◽  
Katalin A Wilkinson
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Antiretroviral Treatment ◽  
Cell Activation ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Immune Memory ◽  
Tuberculosis Antigen

Abstract The reconstitution of Mycobacterium tuberculosis antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in a high tuberculosis endemic area is described. Restoration of the antigen-specific CD4 T-cell subsets mirrored the overall CD4 T-cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known M. tuberculosis sensitization determined by interferon-γ release assay, 12/23 participants had no M. tuberculosis-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T-cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.

scholarly journals Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins

Virology ◽  
2018 ◽  
Vol 516 ◽  
pp. 21-29 ◽  
Author(s):  
Mingce Zhang ◽  
Tanya O. Robinson ◽  
Alexandra Duverger ◽  
Olaf Kutsch ◽  
Sonya L. Heath ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cd4 T Cells ◽  
Regulatory Proteins ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Hiv 1

scholarly journals Responsiveness of HIV-specific CD4 T cells to PD-1 blockade

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 965-974 ◽  
Author(s):  
Filippos Porichis ◽  
Douglas S. Kwon ◽  
Jennifer Zupkosky ◽  
Daniel P. Tighe ◽  
Ashley McMullen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Secretion ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Disease Stage ◽  
T Helper ◽  
The Impact

Abstract Defining the T helper functions impaired by programmed death–1 (PD-1) is crucial for understanding its role in defective HIV control and determining the therapeutic potential of targeting this inhibitory pathway. We describe here the relationships among disease stage, levels of PD-1 expression, and reversibility of CD4 T-cell impairment. PD-L1 blockade in vitro enhanced HIV-specific production of Th0 (IL-2), Th1 (IFN-γ), Th2 (IL-13), and TFH (IL-21) cytokines by CD4 T cells. PD-L1 blockade caused an early increase in cytokine transcription and translation that preceded cell proliferation. Although the impact of PD-L1 blockade on cytokine expression and, to a lesser extent, cell proliferation was associated with markers of disease progression, restoration of cytokine secretion was also observed in most subjects with undetectable viremia. PD-L1 blockade restored cytokine secretion in both PD-1intermediate and PD-1high sorted CD4 T-cell subsets. Compared with PD-1high HIV-specific CD8 T cells, PD-1high HIV-specific CD4 T cells showed lower expression of the inhibitory molecules CD160 and 2B4, demonstrating marked differences in expression of inhibitory receptors between T-cell subsets. These data show that PD-1 impairs HIV-specific T helper responses both by limiting expansion of these cells and by inhibiting effector functions of multiple differentiated CD4 T-cell subsets.

scholarly journals Aging is accompanied by a decrease in the number of naive Tregs

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Filatova ◽  
A Potekhina ◽  
N Radyukhina ◽  
N Ruleva ◽  
T Arefieva
Keyword(s):  
T Cells ◽  
T Cell ◽  
Negative Correlation ◽  
Cd4 T Cells ◽  
Carotid Atherosclerosis ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Absolute Content ◽  
Group Iii ◽  
The Absolute

Abstract Funding Acknowledgements Type of funding sources: None. Background. Age-related changes in the immune system are an important factor contributing to the maintenance of chronic inflammatory status. There are undoubted data on the decrease of the number of T-lymphocytes with age caused by thymus involution, but there are currently no unambiguous data on changes of minor T-cell subpopulations, in particular, regulatory T-cells (Treg). The aim of this study was to analyze the content of effector and regulatory CD4+ T cell subsets in patients with coronary and/or carotid atherosclerosis depending on age. Methods. 111 patients (men, median age 63 (55;69)) with coronary and/or carotid atherosclerosis, without smoking anamnesis, were enrolled.  Mononuclear leuocytes were isolated from blood by gradient centrifugation, and CD4 + CD25high and CD4 + Foxp3+ Treg, CD4 + IL17+ T-helpers (Th) 17 and CD4 + INFγ Th1 were evaluated by direct immunofluorescence and flow cytometry. For intracellular cytokine detection cells were pre-activated in vitro in the presence of PMA/ionomycin/brefeldin A. In 74 patients cells were additionally stained with CD39, CD278, CD45RA Mabs to reveal naïve and primed T-cells. Results. According to age the patients formed three groups: I – <55 y.o. (n = 23), II – 55-64 y.o. (n = 42), III - ≥65 y.o. (n = 46). All patients were taking statins at baseline. The groups were comparable in traditional risk factors of CVD (BMI, arterial hypertension, diabetes mellitus, previous myocardial infarction anamnesis). The absolute content of CD4+ T cells was lower in group III (646.3 (516.0;806.4)) compared to groups I (903.0 (585.6;1113.8), p = 0.03) and II (745.4 (502.2;924.0), p = 0.06). The absolute content of CD4 + CD25high Treg was lower in group III (24.2 (18.4;35.2)) compared to groups I (35.0 (28.7;54.4), p = 0.01) and II (31.0 (21.1;43.6), p = 0.03). There were no differences in Th1, Th17, CD39 + CD45RA- and CD278+ Treg content between groups. A negative correlation was found between age and the content of CD4+ T cells (r= -0.28), CD4 + CD25high Treg (r= -0.27), p < 0.05. A negative correlation was found between age and CD4 + CD25highCD45RA+ Treg (r= -0.24) and CD4 + CD45RA+ T cells (r= -0.36), CD4 + CD45RA+/CD4 + CD45RA- T-cells ratio (r= -0.24), p < 0.05. Conclusion. Here we demonstrate an age-dependent decrease of total CD4+ T cell population and Treg subset in patients with atherosclerosis. The changes observed were primary due to the deficiency of CD45RA+ naïve T cells. The effector cell Th1 and Th17 quantities were at the same levels. Future research will show whether the identified immunological patterns can contribute to the progression of atherosclerosis and other chronic inflammatory diseases.

scholarly journals Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3039
Author(s):  
Mikołaj Nawrocki ◽  
Niels Lory ◽  
Tanja Bedke ◽  
Friederike Stumme ◽  
Björn-Phillip Diercks ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Mouse Model ◽  
Nicotinic Acid ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
T Cell Differentiation ◽  
Cd4 T Cell

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+ mobilizing agent and its inhibition proved to inhibit T-cell activation. However, the impact of the NAADP signaling on CD4+ T-cell differentiation and plasticity and on the inflammation in tissues other than the central nervous system remains unclear. In this study, we used an antagonist of NAADP signaling, trans-Ned 19, to study the role of NAADP in CD4+ T-cell differentiation and effector function. Partial blockade of NAADP signaling in naïve CD4+ T cells in vitro promoted the differentiation of Th17 cells. Interestingly, trans-Ned 19 also promoted the production of IL-10, co-expression of LAG-3 and CD49b and increased the suppressive capacity of Th17 cells. Moreover, using an IL-17A fate mapping mouse model, we showed that NAADP inhibition promotes conversion of Th17 cells into regulatory T cells in vitro and in vivo. In line with the results, we found that inhibiting NAADP ameliorates disease in a mouse model of intestinal inflammation. Thus, these results reveal a novel function of NAADP in controlling the differentiation and plasticity of CD4+ T cells.

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