Faculty Opinions recommendation of Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells.

Hepatitis C virus (HCV) is an important causative agent of liver disease, but factors that determine the resolution or progression of infection are poorly understood. In this study, we suggested that existence of immunosuppressive mechanisms, supported by regulatory T cells and especially the regulatory T cell 1 subset (Tr1), may explain the impaired immune response during infection and thus the fibrosis aggravation to hepatocellular carcinoma (HCC). Using quantitative real-time PCR, we investigated the intra-hepatic presence of Tr1 cells in biopsies from a genotype 1b infected patient followed for an 18-year period from cirrhosis to HCC. We described a significant increase of gene expression in particular for the cytokines IL-10, TGF-β, and their receptors that were perfectly correlated with an increased expression of the Tr1 specific markers (combined expression of CD4, CD18, and CD49b). This was strongly marked since the patient evolved in the pathology and could explain the failure of the treatment. In conclusion, evidence of regulatory T cell installation in the liver of chronically infected patient with cirrhosis and HCC suggests for the first time a key role for these cells in the course of HCV infection.

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

Multiple Sclerosis Journal ◽

10.1177/13524585211003301 ◽

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.

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Multiply restimulated human thymic regulatory T cells express distinct signature regulatory T-cell transcription factors without evidence of exhaustion

Cytotherapy ◽

10.1016/j.jcyt.2021.02.118 ◽

2021 ◽

Author(s):

Keli L. Hippen ◽

Scott N. Furlan ◽

Rahul Roychoudhuri ◽

Ena Wang ◽

Yigang Zhang ◽

...

Keyword(s):

T Cells ◽

Transcription Factors ◽

T Cell ◽

Regulatory T Cells ◽

Regulatory T Cell

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Regulatory T Cells Contribute to Resistance against Lyme Arthritis

Infection and Immunity ◽

10.1128/iai.00160-20 ◽

2020 ◽

Vol 88 (11) ◽

Author(s):

Emily M. Siebers ◽

Elizabeth S. Liedhegner ◽

Michael W. Lawlor ◽

Ronald F. Schell ◽

Dean T. Nardelli

Keyword(s):

T Cells ◽

T Cell ◽

Lyme Disease ◽

Regulatory T Cells ◽

Regulatory T Cell ◽

Interleukin 10 ◽

Lyme Arthritis ◽

Interleukin 17 ◽

Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

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