Effect of CD4+CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis

Longhi, Maria Serena; Ma, Yuanfang; Mitry, Ragai R.; Bogdanos, Dimitrios P.; Heneghan, Michael A.; Cheeseman, Paul; Mieli‐Vergani, Giorgina; Vergani, Diego

doi:10.1016/j.jaut.2005.05.001

Cited by 209 publications

(168 citation statements)

References 40 publications

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“…The outcome of chronic inflammation is the result of a balance between pro-and anti-inflammatory responses in which T regs maintain stable chronic inflammation while preventing fulminant destructive inflammation (31). This is particularly important in liver disease, in which intrahepatic T regs are detected in chronic hepatitis from a variety of causes (5,32,33). The frequency and function of intrahepatic T regs were reported to affect the outcome of chronic infection with hepatitis B and C viruses and to be associated with suppression of the antitumor immune response in hepatocellular carcinoma (4,33).…”

Section: Discussionmentioning

confidence: 99%

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

Weston

Lalor

et al. 2010

The Journal of Immunology

201

185

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Regulatory T cells (Tregs) are found at sites of chronic inflammation where they mediate bystander and Ag-specific suppression of local immune responses. However, little is known about the molecular control of Treg recruitment into inflamed human tissues. We report that up to 18% of T cells in areas of inflammation in human liver disease are forkhead family transcriptional regulator box P3 (FoxP3)+ Tregs. We isolated CD4+CD25+CD127lowFoxP3+ Tregs from chronically inflamed human liver removed at transplantation; compared with blood-derived Tregs, liver-derived Tregs express high levels of the chemokine receptors CXCR3 and CCR4. In flow-based adhesion assays using human hepatic sinusoidal endothelium, Tregs used CXCR3 and α4β1 to bind and transmigrate, whereas CCR4 played no role. The CCR4 ligands CCL17 and CCL22 were absent from healthy liver, but they were detected in chronically inflamed liver where their expression was restricted to dendritic cells (DCs) within inflammatory infiltrates. These DCs were closely associated with CD8 T cells and CCR4+ Tregs in the parenchyma and septal areas. Ex vivo, liver-derived Tregs migrated to CCR4 ligands secreted by intrahepatic DCs. We propose that CXCR3 mediates the recruitment of Tregs via hepatic sinusoidal endothelium and that CCR4 ligands secreted by DCs recruit Tregs to sites of inflammation in patients with chronic hepatitis. Thus, different chemokine receptors play distinct roles in the recruitment and positioning of Tregs at sites of hepatitis in chronic liver disease.

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Section: Discussionmentioning

confidence: 99%

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

Weston

Lalor

et al. 2010

The Journal of Immunology

201

185

View full text Add to dashboard Cite

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“…Total RNA was extracted from 3 × 10 5 cells using TRIzol reagent (Thermo Scientific) and mRNA was reverse transcribed using an iScript cDNA Synthesis kit (Bio-Rad Laboratories) according to the manufacturer's instructions. Primer sequences of human AHR, HMOX1, and FOXP3 and of mouse Hmox1 and Cyp1A1 were as previously described (52)(53)(54)(55)(56). Human IL10 and ENTPD1 primer sequences were as follows: IL10 Forward 5′-TCCTTGCTGGAGGACTTTA-AGGGT-3′ and Reverse 5′-TGTCTGGGTCTTGGTTCTCAGCTT-3′; ENTPD1 Forward 5′-AGGT-GCCTATGGCTGGATTAC-3′ and Reverse 5′-CCAAAGCTCCAAAGGTTTCCT-3′.…”

Section: Quantitative Pcrmentioning

confidence: 99%

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

et al. 2017

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“…However, the IL-15-treated CD3/CD28-activated cells with enhanced regulatory T function may prove useful to prevent autoimmunity, as they also suppressed CD8 þ T-cell response. 36 Further work will be needed to clarify the molecular mechanisms of IL-15-induced T-regulatory function.…”

Section: Discussionmentioning

confidence: 99%

Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4+ T cells

Cheng

2006

Bone Marrow Transplant

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Autologous transfer of anti-CD3/anti-CD28 (CD3/ CD28)-activated CD4 þ T cells may benefit patients receiving autologous stem cell transplant with severe CD4 lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell survival may enhance immune reconstitution in conjunction with adoptive immunotherapy. We investigated the effect of IL-15 on effector and regulatory function of CD3/CD28-activated CD4 þ T cells. IL-15 upregulated CD45RO and CD25 whereas it downregulated CD62L expression of CD3/ CD28-stimulated CD4 þ T cells. Both type 1 (IFN-c, tumor necrosis factor (TNF)-a) and type 2 (IL-5 and IL-10) production by CD3/CD28-activated CD4 þ T cells was further enhanced by IL-15. Co-culture experiments revealed that CD3/CD28-activated CD4 þ T cells downregulated proliferation of autologous peripheral blood lymphocytes (PBLs) and CD8 þ PBL subsets upon TCR ligation, a contact-dependent effect that was further enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining revealed that CD3/CD28 þ IL-15-activated CD4 þ T cells showed increased apoptosis over CD4 þ T cells stimulated with CD3/CD28 alone. Taken together, pretreatment of CD3/ CD28-activated CD4 þ T cells with IL-15 may increase regulatory function but may aggravate activation-induced apoptosis of CD3/CD28 CD4 þ T cells.

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Effect of CD4+CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis

Cited by 209 publications

References 40 publications

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4+ T cells

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