scholarly journals Age-Associated Characteristics of CD4+ T-Cell Composition in Patients with Atherosclerosis

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 277-284
Author(s):  
Anastasiia Yu. Filatova ◽  
Alexandra V. Potekhina ◽  
Tatiana I. Arefieva
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Group Iii ◽  
Cytokine Detection ◽  
Age Related ◽  
Group I ◽  
The Impact

Background. We aimed to analyze the contents of the main CD4+ T-cell subsets in patients with atherosclerosis (AS) depending on age. Methods. Male patients with coronary and/or carotid AS, who are non-smokers, and who are receiving statins were divided into three age groups (I—<55 y.o. (n = 23), II—55–64 y.o. (n = 42), III—≥65 y.o. (n = 46)). Leukocyte phenotyping was performed by direct immunofluorescence and flow cytometry. For intracellular cytokine detection, blood mononuclear cells were pre-activated with phorbol 12-myristate 13-acetate and ionomycin in the presence of an intracellular vesicle transport blocker monensin. Results. The groups did not differ in traditional CVD risk factors and AS severity. The content of CD4+ T-cells was lower in group III and II than in group I. The content of CD4+CD25high Treg was lower in group III than in groups I and II. No differences in the quantities of the primed CD39+CD45RA− and CD278high Treg, CD4+INFγ+ Th1, CD4+IL17+ Th17, and CD4+IL17+INFγ+ Th1/17 were observed. There were negative correlations between the values of CD4+ T-cells, CD4+CD45RA+ T-cells, CD4+CD25high Treg, CD4+CD25highCD45RA+ Treg, and age. Conclusion. In patients with AS, the age-related depletion of naive CD4+ T-cells also extends to the regulatory compartment. This phenomenon should be considered when studying the impact of the immune cells on the progression of AS.

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 – &lt;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 &lt; 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 &lt; 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 Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 260
Author(s):  
Myriam Ben Ben Khelil ◽  
Yann Godet ◽  
Syrine Abdeljaoued ◽  
Christophe Borg ◽  
Olivier Adotévi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cd4 T Cells ◽  
Critical Role ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cancer Therapies ◽  
The Impact

Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.

scholarly journals Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw8330 ◽  
Author(s):  
Yehezqel Elyahu ◽  
Idan Hekselman ◽  
Inbal Eizenberg-Magar ◽  
Omer Berner ◽  
Itai Strominger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Inflammation ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Age Related ◽  
T Cell Phenotypes ◽  
Cell Phenotypes ◽  
Old Mice

Age-associated changes in CD4 T-cell functionality have been linked to chronic inflammation and decreased immunity. However, a detailed characterization of CD4 T cell phenotypes that could explain these dysregulated functional properties is lacking. We used single-cell RNA sequencing and multidimensional protein analyses to profile thousands of CD4 T cells obtained from young and old mice. We found that the landscape of CD4 T cell subsets differs markedly between young and old mice, such that three cell subsets—exhausted, cytotoxic, and activated regulatory T cells (aTregs)—appear rarely in young mice but gradually accumulate with age. Most unexpected were the extreme pro- and anti-inflammatory phenotypes of cytotoxic CD4 T cells and aTregs, respectively. These findings provide a comprehensive view of the dynamic reorganization of the CD4 T cell milieu with age and illuminate dominant subsets associated with chronic inflammation and immunity decline, suggesting new therapeutic avenues for age-related diseases.

scholarly journals The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  
Keyword(s):  
T Cells ◽  
Oxygen Consumption ◽  
T Cell ◽  
Real Time ◽  
Cd4 T Cells ◽  
Cell Metabolism ◽  
Cd4 T Cell ◽  
Autologous Serum ◽  
Cell Phenotype ◽  
The Impact

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

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 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.

scholarly journals Innate IFNγ is essential for systemic Chlamydia control while CD4 T cell-dependent IFNγ production is highly redundant in the female reproductive tract

2020 ◽  
Author(s):  
Miguel A.B. Mercado ◽  
Wuying Du ◽  
Priyangi A. Malaviarachchi ◽  
Jessica I. Gann ◽  
Lin-Xi Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Reproductive Tract ◽  
Early Stage ◽  
Female Reproductive Tract ◽  
Cd4 T Cell ◽  
Bacterial Killing ◽  
Group I ◽  
Deficient Mice

AbstractProtective immunity to the obligate intracellular bacterium Chlamydia is thought to rely on CD4 T cell-dependent IFNγ production. Nevertheless, whether IFNγ is produced by other cellular source during Chlamydia infection and how CD4 T cell-dependent and -independent IFNγ contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFNγ produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal inoculation, IFNγ-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFNγ and CD4 T cells in host defense against Chlamydia. In Rag-deficient mice, IFNγ produced by innate lymphocytes (ILCs) accounted for early bacterial containment and prolonged survival in the absence of adaptive immunity. Although group I ILCs are potent IFNγ producers, we found that mature NK cells and ILC1 were not the sole source for innate IFNγ in response to Chlamydia. T cell adoptive transfer experiments revealed that WT and IFNγ-deficient CD4 T cells were equally capable of mediating effective bacterial killing in the FRT during the early stage of Chlamydia infection. Together, our results revealed that innate IFNγ is essential for preventing systemic Chlamydia dissemination, whereas IFNγ produced by CD4 T cells is largely dispensable at the FRT mucosa.

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.

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