The extent of HLA-DR expression on HLA-DR<sup>+</sup>Tregs allows the identification of patients with clinically relevant borderline rejection

Schaier, Matthias; Seissler, Nicole; Becker, Luis; Schaefer, S.; Schmitt, Edgar; Meuer, Stefan; Hug, Friederike; Sommerer, Claudia; Waldherr, Rüdiger; Zeier, Martin; Steinborn, Andrea

doi:10.1111/tri.12032

Cited by 19 publications

(14 citation statements)

References 35 publications

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“…In particular, the DR high+ memory Tregs were found to be of potential importance for the suppressive activity of the total Treg pool, as these cells were shown to be reduced significantly in kidney transplant patients with acute rejection, compared to non-rejecting patients [23,24]. Surprisingly, we found this relation to be reversed in pregnancy.…”

Section: Cd25mentioning

confidence: 56%

“…Especially for Treg cells, it was shown that the highly activated DR low+ and DR high+ memory Tregs have the highest sup-pressive activity within the total T reg pool in normal healthy control subjects [23]. In particular, the DR high+ memory Tregs were found to be of potential importance for the suppressive activity of the total Treg pool, as these cells were shown to be reduced significantly in kidney transplant patients with acute rejection, compared to non-rejecting patients [23,24]. Surprisingly, we found this relation to be reversed in pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

Schober

Radnai

Spratte

et al. 2014

Clinical and Experimental Immunology

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SummaryPhysiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4 + T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4 + CD127 low+/− CD25 + Treg pool was significantly reduced in GDM patients. The composition of the total Treg pool changed in the way that its percentage of naive CD45RA + Tregs was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR − -memory Tregs was increased significantly in patients with dietary-adjusted GDM, while the percentage of DR low+ and DR high+ memory Tregs was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory Tregs may cause the reduction of the suppressive capacity of the total Treg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.

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Section: Cd25mentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

Schober

Radnai

Spratte

et al. 2014

Clinical and Experimental Immunology

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“…An increased post-transplant sCD30 serum concentration and positive pre-and post-transplant anti-HLA class II reactivities may be useful biomarkers for post-transplant immune monitoring predicting BPAR in pediatric renal transplant recipients [27]. Regulatory T cells (Tregs) were also shown to be involved in the pathogenesis of acute rejection [28]. The determination of the HLA-DR MFI of the HLA-DR(+)-Treg subset allows to discriminate between patients with clinically relevant borderline rejection and patients with subclinical rejection or other causes of transplant failure.…”

Section: Discussionmentioning

confidence: 99%

The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

et al. 2014

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SummaryNon-HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti-angiotensin II type 1-receptor-activating antibodies (anti-AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti-AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti-AT1R antibodies in 117 consecutive renal transplant recipients in pre-and post-transplant screening. Anti-AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti-AT1R(+) group. The patients with anti-AT1R Abs >9 U/ml lost their graft more often. Biopsy-proven AR was described in 4/27 (15%) pts in the anti-AT1R(+) group and 13/90 (14.4%) in the anti-AT1R(À) group, but more severe cases of Banff IIB or antibody-mediated rejection (AMR) were more often observed in anti-AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti-AT1R(+) (P = 0.009). Patients with anti-AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti-AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti-AT1R-positive ones lost the graft. Our study suggests monitoring of anti-AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.

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“…33 HLA-DR 1 Tregs have been previously described as a functionally distinct population with a high suppressive effect that might play a role in organ rejection. [34][35][36] Additionally, earlier publications have shown that CD49d -Tregs are free of contaminating activated T cells and result in purer populations of FoxP3 1 Tregs. 37 The overall frequency of Tregs (regardless of the panel used for their definition) remained stable over time after transplantation, as shown in Supporting Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To further characterize Tregs and their subpopulations, groups were defined on the basis of the surface markers CD45RA and CCR7, and naive Tregs were additionally described as CD45RA + CD62L + . HLA‐DR + Tregs have been previously described as a functionally distinct population with a high suppressive effect that might play a role in organ rejection . Additionally, earlier publications have shown that CD49d – Tregs are free of contaminating activated T cells and result in purer populations of FoxP3 + Tregs …”

Section: Resultsmentioning

confidence: 99%

Comprehensive phenotyping of regulatory T cells after liver transplantation

et al. 2015

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Regulatory T cells (Tregs) play an important role in controlling alloreactivity after solid organ transplantation, but they may also impair antiviral immunity. We hypothesized that the Treg frequency and the Treg phenotype are altered in hepatitis C virus (HCV)-infected recipients of liver transplantation (LT) with possible prognostic implications. Tregs from 141 individuals, including healthy individuals, LT recipients with or without persistent HCV infections, and nontransplant patients with chronic HCV, were studied. A comprehensive phenotypic analysis was performed with multicolor flow cytometry, which included standard Treg markers [CD4 1 , CD25 hi , CD127 -, and FoxP3 1 in addition to HLA DR, CCR7, CD45RA, CD62L, CD49d, CD39, ICOS and LAP-TGFb stainings. Healthy individuals and LT patients displayed similar Treg frequencies and largely comparable Treg phenotypes, which were stable over time after transplantation. In contrast, Tregs with a CD45RA -CCR7 -effector phenotype were enriched in LT recipients with chronic HCV versus HCV-negative transplant patients. HCV infection, rather than LT, altered the expression of functional markers on Tregs. A principal component analysis revealed distinct Treg phenotypes in HCV-infected LT recipients with rejection and patients with recurrent graft HCV. In conclusion, Treg phenotypes are altered in HCV-infected LT patients. An investigation of Tregs may possibly help to distinguish recurrent HCV from graft rejection. Further functional studies are needed to define the role of Tregs in determining the balance between antiviral and allogenic immunity. Liver Transpl 21:381-395, 2015. V C 2015 AASLD.

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The extent of HLA-DR expression on HLA-DR⁺Tregs allows the identification of patients with clinically relevant borderline rejection

Cited by 19 publications

References 35 publications

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Comprehensive phenotyping of regulatory T cells after liver transplantation

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The extent of HLA-DR expression on HLA-DR+Tregs allows the identification of patients with clinically relevant borderline rejection

Cited by 19 publications

References 35 publications

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus

The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Comprehensive phenotyping of regulatory T cells after liver transplantation

Contact Info

Product

Resources

About

The extent of HLA-DR expression on HLA-DR⁺Tregs allows the identification of patients with clinically relevant borderline rejection