Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin and autoimmune dermatoses

Abstract The expandability of CD4+CD25+ regulatory T-cells (Treg) has been shown in vitro and in vivo. Activation of telomerase activity is a prerequisite for clonal expansion and telomere maintenance in T-cells. There is currently no data available on the expression and function of telomerase in proliferating Treg. Analyses of telomere length by flow-FISH, real-time PCR and Southern blotting revealed that Treg isolated from healthy human volunteers have significantly shortened telomeres when compared to CD4+CD25− T-cells. However, telomere length is not further shortened in Treg isolated from the peripheral blood of cancer patients, despite the observation that the regulatory T-cell pool of these patients was significantly enlarged. To gain further insight into maintenance of telomere length of Treg, we induced in vitro proliferation of Treg by stimulation with anti-CD3 and IL-2. This led to a rapid increase of telomerase activity, as determined by PCR-ELISA. However, when we focused on the proliferating fraction of Treg using a sorting strategy based on the dilution of CFSE, we could show a significant telomere shortening in Treg with high proliferative and immmuno-suppressive capacity. Of note, proliferating CFSElow Treg are characterized by high telomerase activity, which however seems to be insufficient to avoid further telomere shortening under conditions of strong in vitro stimulation. In contrast, under conditions of in vivo expansion of Treg in cancer patients, the induction of telomerase activity is likely to compensate for further telomere erosion. These data might be of importance when considering the application of in vitro expanded Treg for the treatment of GvHD or autoimmune diseases, as telomere shortening might be associated with genomic instability.

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392 IL-2, IL-4 and TGF-beta promote the differentiation of IL-9-producing T cells from healthy human skin

Journal of Investigative Dermatology ◽

10.1016/j.jid.2017.07.587 ◽

2017 ◽

Vol 137 (10) ◽

pp. S259

Author(s):

P. Kienzl ◽

P. Hagenbach ◽

R. Polacek ◽

P. Tajpara ◽

M. Mildner ◽

...

Keyword(s):

T Cells ◽

Human Skin ◽

Tgf Beta ◽

Healthy Human

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The Responsiveness of Bee Venom Phospholipase A2 on Regulatory T Cells Correlates with the CD11c+CD206+Population in Human Peripheral Blood Mononuclear Cells

Toxins ◽

10.3390/toxins13100717 ◽

2021 ◽

Vol 13 (10) ◽

pp. 717

Author(s):

Heejin Jo ◽

Hyunjung Baek ◽

Seon-Young Park ◽

Bonhyuk Goo ◽

Woo-Sang Jung ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Phospholipase A2 ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Bee Venom ◽

Control Group ◽

Therapeutic Effects ◽

Healthy Human

Bee venom phospholipase A2 (bvPLA2) has been reported to have therapeutic effects such as neuroprotection, anti-inflammation, anti-nociception, anti-cancer properties, caused by increasing regulatory T cells (Tregs). The mechanism of Tregs modulation by bvPLA2 has been demonstrated by binding with the mannose receptor, CD206 in experimental models of several diseases. However, it remains unknown whether this mechanism can also be applied in human blood. In this study, we collected peripheral blood samples from healthy donors and analyzed the percentages of monocyte-derived dendritic cells with CD206 (CD206+ DCs) before expansion, the proportion of Tregs, and the subpopulations after expansion treated with bvPLA2 or PBS using flow cytometry and the correlations among them. The percentage of Tregs tended to be higher in the bvPLA2 group than in the control group. There were significant positive correlations between the CD206 population in hPBMC and the proportions of Tregs treated with bvPLA2, especially in the Treg fold change comparing the increase ratio of Tregs in bvPLA2 and in PBS. These findings indicate that bvPLA2 increased the proportion of Tregs in healthy human peripheral blood and the number of CD206+ DCs could be a predictor of the bvPLA2 response of different individuals.

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Faculty Opinions recommendation of IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1067049.520028 ◽

2007 ◽

Author(s):

Thomas Nutman

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Human Skin ◽

Dermal Fibroblasts

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Carica papaya increases regulatory T cells and reduces IFN-γ+CD4+ T cells in healthy human subjects

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201100087 ◽

2011 ◽

Vol 55 (5) ◽

pp. 803-806 ◽

Cited By ~ 18

Author(s):

Maha Abdullah ◽

Pei-Shin Chai ◽

Chiew-Yee Loh ◽

Mun-Yee Chong ◽

Huai-Wei Quay ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Cd4 T Cells ◽

Carica Papaya ◽

Human Subjects ◽

Healthy Human ◽

Healthy Human Subjects ◽

Ifn Γ

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Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

Brazilian Oral Research ◽

10.1590/1807-3107bor-2016.vol30.0130 ◽

2016 ◽

Vol 30 (1) ◽

Cited By ~ 2

Author(s):

Fernando Antonio Portela da CUNHA FILHO ◽

Maria Cássia Ferreira de AGUIAR ◽

Lélia Batista de SOUZA ◽

Leão PEREIRA PINTO ◽

Gustavo Pina GODOY ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Squamous Cell ◽

Immunohistochemical Analysis ◽

Squamous Cell Carcinomas ◽

Lower Lip

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Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Frontiers in Immunology ◽

10.3389/fimmu.2021.642711 ◽

2021 ◽

Vol 12 ◽

Author(s):

Astrid Hendriks ◽

Malgorzata Ewa Mnich ◽

Bruna Clemente ◽

Ana Rita Cruz ◽

Simona Tavarini ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cells ◽

Human Skin ◽

Ex Vivo ◽

Functional Characterization ◽

T Cell Response ◽

Skin Microbiome ◽

Entry Site ◽

Healthy Human ◽

Skin Explants

The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. Staphylococcus aureus is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against S. aureus infection, however genetic and experimental evidence has shown that CD4+ T cells play a key role in orchestrating a protective anti-S. aureus immune response. A high S. aureus-specific memory CD4+ T cell response has been reported in the blood of healthy subjects. Since T cells are more abundant in the skin than in blood, we hypothesized that S. aureus-specific CD4+ T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4+ T cells and production of IL-17A, IL-22, IFN-γ and TNF-β by cells isolated from abdominal skin explants in response to heat-killed S. aureus. Remarkably, these cytokines were produced also during an ex vivo epicutaneous S. aureus infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4+ T cells present at barrier sites such as the skin, a primary entry site for S. aureus. Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.

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Antigen-bearing immature dendritic cells induce peptide-specific CD8+ regulatory T cells in vivo in humans

Blood ◽

10.1182/blood.v100.1.174 ◽

2002 ◽

Vol 100 (1) ◽

pp. 174-177 ◽

Cited By ~ 262

Author(s):

Madhav V. Dhodapkar ◽

Ralph M. Steinman

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Cd8 T Cells ◽

Cell Function ◽

Human Subjects ◽

Interferon Γ ◽

Healthy Human ◽

Immature Dendritic Cells

Abstract Regulatory T cells (TRs) can suppress the function of other effector T cells in the setting of autoimmunity, transplantation, and resistance to tumors. The mechanism for the induction of TRs has not been defined. We previously reported that an injection of immature dendritic cells (DCs) pulsed with influenza matrix peptide (MP) led 7 days later to antigen-specific silencing of effector T-cell function in the blood of 2 healthy human subjects. Here, we found that interferon-γ–producing effectors return by 6 months. Importantly, in mixing experiments, CD8+ T cells from the sample obtained 7 days after injection could suppress MP-specific effectors obtained before injection and those in recovery samples. This suppression or regulation was specific for the immunizing peptide (MP) and cell-dose dependent, and it required contact between the 2 samples. These data show the capacity of immature DCs to induce antigen-specific regulatory CD8+ T cells in humans.

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CD4+CD25+ Regulatory T Cells in Intracranial Thrombi Are Inversely Correlated with Hemorrhagic Transformation after Thrombectomy: A Clinical-Immunohistochemical Analysis of Acute Ischemic Stroke

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/3143248 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Li Gong ◽

Xiaoran Zheng ◽

Weiyan Zhang ◽

Zhongwen Shu ◽

Haichao Wang ◽

...

Keyword(s):

T Cells ◽

Ischemic Stroke ◽

Regulatory T Cells ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Immunohistochemical Analysis ◽

Treg Cells ◽

Hemorrhagic Transformation ◽

Pathological Process ◽

Additional Information

Mechanical thrombectomy is not only effective for managing patients with acute ischemic stroke (AIS), but it also enables a valuable histological analysis of thrombi. Previous studies indicated that regulatory T cells (Treg) adoptive transfer might alleviate the hemorrhagic transformation. However, whether Treg in intracranial thrombi correlates with hemorrhagic transformation after mechanical thrombectomy remains unclear. This study mainly analyzed the colocation of Treg markers in serial thrombus sections stained serially for CD4 and CD25 in groups of hemorrhagic or nonhemorrhagic transformation. Second, to investigate whether these immunohistochemical parameters could provide any additional information beyond hemorrhagic transformation, we compared the overlap between Treg markers among other groups, such as functional outcomes, stroke subtypes, and gender. Our results showed that the number of CD4+CD25+ Treg cells was lower in the hemorrhagic transformation thrombi than in the nonhemorrhagic group ( p < 0.001 ) but there were no significant differences otherwise. The present finding of CD4+CD25+ Treg cell reductions in thrombi associated with hemorrhagic transformation provides the histological evidence supporting that thromboinflammation might involve in the pathological process of an acute stroke after mechanical thrombectomy.

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