Impairment of CD4+CD25+ regulatory T-cells in autoimmune liver disease

Longhi, Maria Serena; Ma, Yuanfang; Bogdanos, Dimitrios P.; Cheeseman, Paul; Mieli‐Vergani, Giorgina; Vergani, Diego

doi:10.1016/j.jhep.2004.03.008

Cited by 367 publications

(309 citation statements)

References 45 publications

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“…Our findings are compatible with recent reports suggesting a potential role for Treg in hepatic immune tolerance. 14,15 The frequency of intrahepatic CD25 ϩ T cells in humans has been reported to be approximately 1% to 2% 15 ; we find compatible frequencies of 2% to 4% of the intrahepatic lymphocytes and 15% to 20% of the intrahepatic CD4 ϩ T cells in mouse (not shown). Thus, the numbers of intrahepatic CD25 ϩ T cells seem sufficient to regulate hepatic immune responses.…”

Section: Discussionsupporting

confidence: 47%

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Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

et al. 2005

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U nder physiological conditions, the liver is basically free of inflammation and the resident antigen-presenting cells (APC) of the liver are believed to actively participate in the maintenance of hepatic immune tolerance. 1 Indeed, the most prevalent professional APC in liver, liver sinusoidal endothelial cells (LSEC) and Kupffer cells (KC), 2,3 have been shown to actively induce immune tolerance. 2,4,5 In addition, hepatocytes, which can upregulate expression of class II molecules of the major histocompatibility complex (MHC II) during hepatitis 6 and may then serve as APC for CD4 ϩ T lymphocytes, 7 also have been implicated in the induction of immune tolerance. 8 Nevertheless, rapid infiltration of the liver with inflammatory cells is induced during infection. However, the mechanisms that mediate the transition from hepatic immune tolerance to hepatic inflammation are not clear.CD4 ϩ CD25 ϩ regulatory T cells (Treg) are important mediators of peripheral immune tolerance: Treg can suppress the activation of autoreactive CD4 ϩ and CD8 ϩ T cells [9][10][11] and also control immune responses during infection. 12,13 Whether Treg are involved in the maintenance of hepatic immune tolerance is not clear; however, recent reports indicate that Treg indeed may suppress hepatic immunity to autoantigen 14 or virus. 15 Thus, it is likely that local suppressive Treg activity needs to be attenuated before liver inflammation can be induced.It has been reported recently that splenic dendritic cells have the capacity to regulate the suppressive activity of Treg 16 : normally, dendritic cells stimulate Treg-mediated suppression; however, in response to microbial stimuli, like lipopolysaccharide (LPS) or immune-stimulatory oli-

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Section: Discussionsupporting

confidence: 47%

“…12,13 Whether Treg are involved in the maintenance of hepatic immune tolerance is not clear; however, recent reports indicate that Treg indeed may suppress hepatic immunity to autoantigen 14 or virus. 15 Thus, it is likely that local suppressive Treg activity needs to be attenuated before liver inflammation can be induced.…”

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confidence: 99%

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

et al. 2005

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“…Though the expression of CD45RO and CTLA-4/CD152 are also characteristics of CD4 ϩ CD25 ϩ Treg (15), the forkhead/winged helix transcription factor (FoxP3) has been demonstrated to be a unique marker restricted to the Treg (16). CD4 ϩ CD25 ϩ Treg are implicated in a range of disease states including cancer (17)(18)(19)(20), allograft rejection (21,22), allergy (23), autoimmune diseases (24,25), and infectious diseases (26 -28). Emerging evidence support the hypothesis that pathogenesis of persistent virus infections may be directly related to the levels of circulating CD4 ϩ CD25 ϩ Treg or to the balance of the Treg vs effector T cells.…”

Section: H Epatitis B Virus (Hbv)mentioning

confidence: 99%

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Jin

et al. 2006

The Journal of Immunology

407

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CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4+CD25+ Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3+-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+ Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4+CD25+ Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN-γ production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4+CD25+ Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.

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“…9 A key player in hepatic immune regulation that has recently emerged is the lymphocyte subpopulation known as regulatory T cells (Tregs). 10 Tregs are a group of heterogeneous T cells that are actively engaged in the negative control of a variety of physiological and pathological immune responses, including transplant tolerance, 11 viral hepatitis, 12 autoimmune hepatitis, 13 and hepatocellular carcinoma. 14 Tregs usually coexpress CD4 and CD25 with other surface markers that are not specific for this subpopulation.…”

mentioning

confidence: 99%

A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury

et al. 2007

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Impairment of CD4+CD25+ regulatory T-cells in autoimmune liver disease

Cited by 367 publications

References 45 publications

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury

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