Dataset Information

CD4?CD25?Foxp3? T cells: a marker for lupus nephritis?

ABSTRACT:

Introduction

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, which can affect different organs. Increased proportions of CD4?CD25-Foxp3? T cells have been described in SLE patients. The exact role of this cell population in SLE patients still remains unclear. We therefore analyzed this T cell subset in a large cohort of SLE patients with different organ manifestations.

Methods

Phenotypic analyses, proportions and absolute cell numbers of CD4?CD25-Foxp3? T cells were determined by flow cytometry (FACS) in healthy controls (HC) (n?=?36) and SLE patients (n?=?61) with different organ manifestations. CD4?CD25?Foxp3? T cells were correlated with clinical data, the immunosuppressive therapy and different disease activity indices. In patients with active glomerulonephritis, CD4?CD25?Foxp3? T cells were analyzed in urine sediment samples. Time course analyses of CD4?CD25?Foxp3? T cells were performed in patients with active disease activity before and after treatment with cyclophosphamide and prednisone.

Results

CD4?CD25?Foxp3? T cells were significantly increased in active SLE patients and the majority expressed Helios. Detailed analysis of this patient cohort revealed increased proportions of CD4?CD25?Foxp3? T cells in SLE patients with renal involvement. CD4?CD25?Foxp3? T cells were also detected in urine sediment samples of patients with active glomerulonephritis and correlated with the extent of proteinuria.

Conclusion

CD4?CD25?Foxp3? T cells resemble regulatory rather than activated T cells. Comparative analysis of CD4?CD25?Foxp3? T cells in SLE patients revealed a significant association of this newly described cell population with active nephritis. Therefore CD4?CD25?Foxp3? T cells might serve as an important tool to recognize and monitor SLE patients with renal involvement.

SUBMITTER: Bonelli M

PROVIDER: S-EPMC4060257 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD4⁺CD25⁻Foxp3⁺ T cells: a marker for lupus nephritis?

Bonelli Michael M Göschl Lisa L Blüml Stephan S Karonitsch Thomas T Steiner Carl-Walter CW Steiner Günter G Smolen Josef S JS Scheinecker Clemens C

Arthritis research & therapy 20140428 2

<h4>Introduction</h4>Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, which can affect different organs. Increased proportions of CD4⁺CD25-Foxp3⁺ T cells have been described in SLE patients. The exact role of this cell population in SLE patients still remains unclear. We therefore analyzed this T cell subset in a large cohort of SLE patients with different organ manifestations.<h4>Methods</h4>Phenotypic analyses, proportions and absolute cell numbers of CD4⁺CD25-Foxp3⁺ T ...[more]

PMID: 24774748

Similar Datasets

Project description:ObjectiveThe approximately 45-cM insulin-dependent diabetes 9 (Idd9) region on mouse chromosome 4 harbors several different type 1 diabetes-associated loci. Nonobese diabetic (NOD) mice congenic for the Idd9 region of C57BL/10 (B10) mice, carrying antidiabetogenic alleles in three different Idd9 subregions (Idd9.1, Idd9.2, and Idd9.3), are strongly resistant to type 1 diabetes. However, the mechanisms remain unclear. This study aimed to define mechanisms underlying the type 1 diabetes resistance afforded by B10 Idd9.1, Idd9.2, and/or Idd9.3.Research design and methodsWe used a reductionist approach that involves comparing the fate of a type 1 diabetes-relevant autoreactive CD8(+) T-cell population, specific for residues 206-214 of islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP(206-214)), in noncongenic versus B10 Idd9-congenic (Idd9.1 + Idd9.2 + Idd9.3, Idd9.2 + Idd9.3, Idd9.1, Idd9.2, and Idd9.3) T-cell receptor (TCR)-transgenic (8.3) NOD mice.ResultsMost of the protective effect of Idd9 against 8.3-CD8(+) T-cell-enhanced type 1 diabetes was mediated by Idd9.1. Although Idd9.2 and Idd9.3 afforded some protection, the effects were small and did not enhance the greater protective effect of Idd9.1. B10 Idd9.1 afforded type 1 diabetes resistance without impairing the developmental biology or intrinsic diabetogenic potential of autoreactive CD8(+) T-cells. Studies in T- and B-cell-deficient 8.3-NOD.B10 Idd9.1 mice revealed that this antidiabetogenic effect was mediated by endogenous, nontransgenic T-cells in a B-cell-independent manner. Consistent with this, B10 Idd9.1 increased the suppressive function and antidiabetogenic activity of the FoxP3(+)CD4(+)CD25(+) T-cell subset in both TCR-transgenic and nontransgenic mice.ConclusionsA gene(s) within Idd9.1 regulates the development and function of FoxP3(+)CD4(+)CD25(+) regulatory T-cells and, in turn, the activation of CD8(+) effector T-cells in the pancreatic draining lymph nodes, without affecting their development or intrinsic diabetogenic potential.