Presence of <scp>HLA</scp>‐<scp>DR</scp> Molecules and <i><scp>HLA</scp>‐<scp>DRB</scp>1 </i><scp>mRNA</scp> in Circulating <scp>CD</scp>4<sup>+</sup> T Cells

Revenfeld, Anne Louise; Steffensen, Rudi; Pugholm, Lotte Hatting; Jørgensen, Maléne Møller; Stensballe, Allan; Varming, Kim

doi:10.1111/sji.12462

Cited by 17 publications

(12 citation statements)

References 61 publications

(89 reference statements)

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“…In the case of CD25 and CTLA-4, these two markers displayed a positive correlation for a part of the CD3+ CD4+ HLA-DR+ cells ( Figure 2 A, top panel). However, the non-uniform correlation demonstrated how the CD3+ CD4+ HLA-DR+ T cells were a heterogeneous cell population, which we have also previously observed [ 32 ]. Like CTLA-4, PD-1 has an essential role in T cell inhibition and consequently also in peripheral tolerance [ 39 , 40 ].…”

Section: Discussionsupporting

confidence: 69%

“…Initially, the CD3+ CD4+ HLA-DR+ T cells were identified ( Figure 1 A), using a fluorescence minus one (FMO)-approach [ 31 ]. As previously described, this enables a less user-biased placement of a positive gate, when a marker is expressed continuously, such as HLA-DR on CD3+ CD4+ T cells [ 32 ]. For the three culture samples, the levels of CD3+ CD4+ HLA-DR+ T cells were relatively comparable, although the fraction of these T cells was highest in the contact-dependent MLC ( Figure 1 B).…”

Section: Resultsmentioning

confidence: 99%

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Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Revenfeld

Bæk

Jørgensen

et al. 2017

IJMS

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Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated. Moreover, a functional phenotype was established for these T cells. It was demonstrated that APCs were essential for HLA-DR on CD3+ CD4+ T cells. Additionally, a regulatory T cell phenotype was induced in CD3+ CD4+ HLA-DR+ responder T cells with an expression of CD25, CTLA-4, CD62L, PD-1, and TNFRII. This phenotype was induced both with and without physical T cell:APC contact, which could reveal novel indications about its functionality. To further investigate contact-independent communication, a phenotype of the small cell-derived vesicles from the MLCs was determined. Yet heterogeneous, this vesicle phenotype displayed contact-dependent differences, providing clues about their intended function in cellular communication.

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Section: Discussionsupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Revenfeld

Bæk

Jørgensen

et al. 2017

IJMS

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“…The presence of HLA-DR was not confined to activated CD4+ and CD8+ T cells [14]. Nagafuchi et al [15] studied immunophenotyping of peripheral blood mononuclear cells on RA patients with HLA-DRB1genotype and found the frequency of memory CXCR4+CD4+ T cells was significantly related to severity of disease.…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

Zong

Han

et al. 2016

Oncotarget

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Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age=18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis.

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“…The eTreg subset expresses several surface markers, including the human major histocompatibility complex class II isotype HLA‐DR 32 . HLA‐DR, which is currently used as an activation marker for T cells, 33 is associated with enhanced suppressive activity within the eTreg subset 34 …”

Section: Discussionmentioning

confidence: 99%

HLA‐DR⁺ CD45RAˉ Tregs and CD28ˉ Treg‐like cells: Potential immunologic biomarkers for reproductive aging

Muyayalo

Song

Liu

et al. 2022

American J Rep Immunol

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Problem This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging. Method This prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential. Results The percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells than those at 20–29, 30–34, and 35–39 years old. Age positively correlated with FSH levels and the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA‐DR+ CD45RAˉ Tregs and FSH levels, whereas an inverse correlation was found between those of HLA‐DR+ CD45RAˉ Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28ˉ Treg‐like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells above reference value ranges were assigned to the low prognosis groups. Conclusion These findings suggest that HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.

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Presence of HLA‐DR Molecules and HLA‐DRB1 mRNA in Circulating CD4⁺ T Cells

Cited by 17 publications

References 61 publications

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

HLA‐DR⁺ CD45RAˉ Tregs and CD28ˉ Treg‐like cells: Potential immunologic biomarkers for reproductive aging

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Presence of HLA‐DR Molecules and HLA‐DRB1 mRNA in Circulating CD4+ T Cells

Cited by 17 publications

References 61 publications

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells: Potential immunologic biomarkers for reproductive aging

Contact Info

Product

Resources

About

Presence of HLA‐DR Molecules and HLA‐DRB1 mRNA in Circulating CD4⁺ T Cells

HLA‐DR⁺ CD45RAˉ Tregs and CD28ˉ Treg‐like cells: Potential immunologic biomarkers for reproductive aging