scholarly journals Advances in the Study on the Relationship between Regulatory T cells and Human Papilloma Viral Infection

2016 ◽  
Vol 5 (3) ◽  
pp. 81-86
Author(s):  
Yuting Wang
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Cells ◽  
Treg Cells ◽  
Hpv Infection ◽  
Clinical Applications ◽  
Regulatory Cells ◽  
Papilloma Virus ◽  
The Relationship ◽  
Human Papilloma Viral

AbstractRegulatory T cells (Treg cells) are a group of negative regulatory cells that include non-specific immune regulation CD4+T cells. Treg cells inhibit the function of other immune cells. CD4+CD25+FOXP3+is a Treg cell that is co-expressed by CD25and FOXP3. The expression of Treg cells is up-regulated in the focal microenvironment and peripheral blood of patients infected with human papilloma virus (HPV). Further studies on Treg cells indicate that their potential clinical applications in the treatment of HPV infection.

scholarly journals The Complex Role of Regulatory T Cells in Immunity and Aging

2021 ◽  
Vol 11 ◽  
Author(s):  
Lourdes Rocamora-Reverte ◽  
Franz Leonard Melzer ◽  
Reinhard Würzner ◽  
Birgit Weinberger
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Γδt Cells ◽  
Cell Functions ◽  
Age Related ◽  
Self Antigens

The immune system is a tightly regulated network which allows the development of defense mechanisms against foreign antigens and tolerance toward self-antigens. Regulatory T cells (Treg) contribute to immune homeostasis by maintaining unresponsiveness to self-antigens and suppressing exaggerated immune responses. Dysregulation of any of these processes can lead to serious consequences. Classically, Treg cell functions have been described in CD4+ T cells, but other immune cells also harbour the capacity to modulate immune responses. Regulatory functions have been described for different CD8+ T cell subsets, as well as other T cells such as γδT cells or NKT cells. In this review we describe the diverse populations of Treg cells and their role in different scenarios. Special attention is paid to the aging process, which is characterized by an altered composition of immune cells. Treg cells can contribute to the development of various age-related diseases but they are poorly characterized in aged individuals. The huge diversity of cells that display immune modulatory functions and the lack of universal markers to identify Treg make the expanding field of Treg research complex and challenging. There are still many open questions that need to be answered to solve the enigma of regulatory T cells.

scholarly journals Frequency of CD4+ regulatory T cells, CD8+ T cells, and human papilloma virus infection in Egyptian Women with breast cancer

2020 ◽  
Vol 34 ◽  
pp. 205873842096682
Author(s):  
Amany M Tawfeik ◽  
Ahmed Mora ◽  
Ahmed Osman ◽  
Manar M Moneer ◽  
Nabila El-Sheikh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Human Papilloma Virus ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Early Stage ◽  
Hpv Infection ◽  
Papilloma Virus ◽  
Egyptian Women

Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment of breast cancer (BC) patients and may play a role in the progression of BC. High-risk human papilloma virus (HR-HPV) has a causal role in cervical, head, and neck tumors but the role of HR-HPV in evoking neoplasia in BC is still unclear. In this study we assessed the prevalence of CD4+CD25+ FOXP3+ regulatory T cells (CD4+Tregs) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL), and 20 healthy volunteers (HV). HR-HPV genotypes type 16, 18, and 31 were investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HR-HPV was detected in 4/20 (20%) and 0/15 (0%) BC and BBL patients respectively. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, ( P < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III BC compared to early stage I and II BC ( P = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These results lead us to postulate that the association between the frequency of CD4+ Tregs and CD8+ T cells in the peripheral blood may be a prognostic or predictive parameter in Egyptian women with BC. In addition, HR-HPV infection may be implicated in the development of some types of BC in Egyptian women.

scholarly journals The relationship between human thymus-derived regulatory T cells, TGF-β-induced regulatory T cells and conventional CD4+ T cells as revealed by proteomics

2021 ◽  
Author(s):  
Mark Mensink ◽  
Ellen Schrama ◽  
Maartje van den Biggelaar ◽  
Derk Amsen ◽  
Jannie Borst ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Protein Expression ◽  
Treg Cell ◽  
Ex Vivo ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Cell Populations ◽  
The Relationship

The CD4+ regulatory T (Treg) cell lineage, as defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. In human, naive tTreg cells can be purified from blood, but occur in low abundance, while effector pTreg and tTreg cell populations cannot be purified for lack of discriminating cell surface markers. Therefore, studies often employ TGF-β-induced (i)Treg cells that are generated from CD4+ conventional T (Tconv) cells in vitro. Here, we describe the relationship of iTreg cells to tTreg and Tconv cells, as optimally purified from human blood. Global proteomic analysis revealed that iTreg, tTreg and Tconv cell populations each have a unique protein expression pattern. We next used as a benchmark a previously defined proteomic signature that discerns ex vivo naive and effector phenotype Treg cells from Tconv cells and reflects unique Treg cell properties. This Treg cell core signature was largely absent from iTreg cells, while clearly present in simultaneously analyzed tTreg cells. In addition, we used a proteomic signature that distinguishes ex vivo effector Treg cells from Tconv cells and naive Treg cells. This effector Treg cell signature was partially present in iTreg cells. Thus, iTreg cells are distinct from tTreg cells and largely lack the common Treg cell proteomic signature. However, they do have certain protein expression features in common with ex vivo effector Treg cells. These data demonstrate the utility of the core and effector Treg cell signatures as tools to define Treg cell populations and encourage the use of ex vivo Treg cells for functional analyses.

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

scholarly journals Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Ding ◽  
Rajneesh Malhotra ◽  
Tomas Ottosson ◽  
Magnus Lundqvist ◽  
Aman Mebrahtu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Secreted Proteins ◽  
External Stimulation ◽  
Marker Proteins ◽  
Positive Regulators ◽  
Conformational Model

AbstractRegulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

scholarly journals The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Positive Association ◽  
Tumor Stage ◽  
Melanoma Cells ◽  
Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

scholarly journals Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Cristian Doñas ◽  
Macarena Fritz ◽  
Valeria Manríquez ◽  
Gabriela Tejón ◽  
María Rosa Bono ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Trichostatin A ◽  
Gene Promoter ◽  
Treg Cells ◽  
Specific Subset ◽  
Global Increase ◽  
And Function ◽  
H3 Acetylation

Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that thefoxp3gene promoter becomes hyperacetylated inin vitrodifferentiated Tregs compared to naïve CD4+T cells. We also show that the histone deacetylase inhibitor TSA stimulated thein vitrodifferentiation of naïve CD4+T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+Treg cells.

scholarly journals The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6499-6505 ◽  
Author(s):  
Edgardo D. Carosella ◽  
Silvia Gregori ◽  
Joel LeMaoult
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Recent Work ◽  
Large Body ◽  
Regulatory Cells ◽  
Individual Effects ◽  
The Individual ◽  
Key Aspects ◽  
Antigen Presenting

Abstract Myeloid antigen-presenting cells (APCs), regulatory cells, and the HLA-G molecule are involved in modulating immune responses and promoting tolerance. APCs are known to induce regulatory cells and to express HLA-G as well as 2 of its receptors; regulatory T cells can express and act through HLA-G; and HLA-G has been directly involved in the generation of regulatory cells. Thus, interplay(s) among HLA-G, APCs, and regulatory cells can be easily envisaged. However, despite a large body of evidence on the tolerogenic properties of HLA-G, APCs, and regulatory cells, little is known on how these tolerogenic players cooperate. In this review, we first focus on key aspects of the individual relationships between HLA-G, myeloid APCs, and regulatory cells. In its second part, we highlight recent work that gathers individual effects and demonstrates how intertwined the HLA-G/myeloid APCs/regulatory cell relationship is.

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