Elevated CD4+/CD25+ T-cell Frequency and Function During Hepatitis C Virus Recurrence After Liver Transplantation

Perrella, Alessandro; Arenga, G.; Pisaniello, D.; Rampone, Bernardino; Costanzo, Giovan Giuseppe Di; Atripaldi, Luigi; Esposito, Ciro; Florio, E. Di; Perrella, Oreste; Cuomo, O.

doi:10.1016/j.transproceed.2009.01.112

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…This suggests that CD4 + Foxp3 + Tregs elicit dual-phased roles during the progression of JEV-induced neurological disorders. More importantly, Treg induction during a viral infection is considered to be a detrimental response that promotes virus persistence without benefits to the host [59], [60]. One trivial explanation of CD4 + Foxp3 + Treg role is that initially low number of CD4 + Foxp3 + Tregs in TLR4 −/− mice may promote the expansion of effector CD4 + and CD8 + T cells specific for JEV antigen as well as innate immune responses, thereby inducing enhanced anti-viral response and virus-specific CTL to promote early viral clearance.…”

Section: Discussionmentioning

confidence: 99%

Distinct Dictation of Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality via Triggering TLR3 and TLR4 Signal Pathways

et al. 2014

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Japanese encephalitis (JE) is major emerging neurologic disease caused by JE virus. To date, the impact of TLR molecules on JE progression has not been addressed. Here, we determined whether each TLR modulates JE, using several TLR-deficient mouse strains (TLR2, TLR3, TLR4, TLR7, TLR9). Surprisingly, among the tested TLR-deficient mice there were contrasting results in TLR3−/− and TLR4−/− mice, i.e. TLR3−/− mice were highly susceptible to JE, whereas TLR4−/− mice showed enhanced resistance to JE. TLR3 ablation induced severe CNS inflammation characterized by early infiltration of inflammatory CD11b+Ly-6Chigh monocytes along with profoundly increased viral burden, proinflammatory cytokine/chemokine expression as well as BBB permeability. In contrast, TLR4−/− mice showed mild CNS inflammation manifested by reduced viral burden, leukocyte infiltration and proinflammatory cytokine expression. Interestingly, TLR4 ablation provided potent in vivo systemic type I IFN innate response, as well as ex vivo type I IFN production associated with strong induction of antiviral PRRs (RIG-I, MDA5), transcription factors (IRF-3, IRF-7), and IFN-dependent (PKR, Oas1, Mx) and independent ISGs (ISG49, ISG54, ISG56) by alternative activation of IRF3 and NF-κB in myeloid-derived DCs and macrophages, as compared to TLR3−/− myeloid-derived cells which were more permissive to viral replication through impaired type I IFN innate response. TLR4 ablation also appeared to mount an enhanced type I IFN innate and humoral, CD4+ and CD8+ T cell responses, which were mediated by altered immune cell populations (increased number of plasmacytoid DCs and NK cells, reduced CD11b+Ly-6Chigh monocytes) and CD4+Foxp3+ Treg number in lymphoid tissue. Thus, potent type I IFN innate and adaptive immune responses in the absence of TLR4 were closely coupled with reduced JE lethality. Collectively, these results suggest that a balanced triggering of TLR signal array by viral components during JE progression could be responsible for determining disease outcome through regulating negative and positive factors.

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Section: Discussionmentioning

confidence: 99%

Distinct Dictation of Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality via Triggering TLR3 and TLR4 Signal Pathways

et al. 2014

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“…Peripheral CD4+ CD25+ T-cells were also found to be elevated soon after a post-transplant HCV recurrence and they had a greater suppressive capacity than CD4+ CD25+ T-cells from healthy donors [48]. Interestingly, the levels and suppressive potential of CD4+ CD25+ T-cells from patients with acute hepatitis C were similar, suggesting that HCV reinfection reproduces the same pattern as the primary infection in terms of Treg induction.…”

Section: Treg and Hcv Recurrence After Liver Transplantationmentioning

confidence: 90%

“…In vivo, the immunization of mice using an adenoviral vector containing HCV core protein enhances CD4+ and CD8+ Treg expressing CD25 and FoxP3 [47]. Furthermore, numerous reports have indicated that Treg from HCV-infected patients have greater suppressive ability than Treg isolated from healthy donors [18,31,34,48]. However, the ability of HCV to infect Treg and eventually increase their suppressive properties still needs to be formally demonstrated.…”

Section: Hcv Infection and Tregmentioning

confidence: 99%

Role of regulatory T-cells during hepatitis C infection: From the acute phase to post-transplantation recurrence

Barjon

Dahlqvist

Calmus

et al. 2015

Digestive and Liver Disease

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Hepatitis C viral infection persists and becomes chronic in a majority of affected individuals. Numerous factors have been described to explain how the virus manages to escape the host immune system. One important escape mechanism is the increase in regulatory T cells induced by the virus. In this review, we will focus on the status of regulatory T cells throughout the natural history of hepatitis C infection and after liver transplantation. The molecular mechanisms involved in increasing the number of regulatory T cells are also discussed, as are data regarding the impact of regulatory T-cells on hepatic fibrosis in the context of hepatitis C viral infection.

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“…Emerging evidence suggest that regulatory T cells may play an integral role. There is an enhanced expression of regulatory T cells in nontransplant individuals with HCV (41–43). Indeed, this association persists after liver transplantation and may be one of the paramount means for rapid disease progression in transplant recipients.…”

mentioning

confidence: 99%

Major Challenges Limiting Liver Transplantation in the United States

Wertheim

Petrowsky

Saab

et al. 2011

American Journal of Transplantation

155

117

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Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma.

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Elevated CD4+/CD25+ T-cell Frequency and Function During Hepatitis C Virus Recurrence After Liver Transplantation

Cited by 10 publications

References 16 publications

Distinct Dictation of Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality via Triggering TLR3 and TLR4 Signal Pathways

Distinct Dictation of Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality via Triggering TLR3 and TLR4 Signal Pathways

Role of regulatory T-cells during hepatitis C infection: From the acute phase to post-transplantation recurrence

Major Challenges Limiting Liver Transplantation in the United States

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