Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen

Lau, George; Suri, Deepak; Liang, Raymond; Rigopoulou, Eirini I.; Thomas, Mark G.; Mullerova, Ivana; Nanji, Amin A.; Yuen, Siu‐Tsan; Williams, Roger; Naoumov, Nikolai V.

doi:10.1053/gast.2002.31887

Cited by 167 publications

(139 citation statements)

References 35 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…[27][28][29][30][31] This immune response may be suppressed by the increased presence of T reg found in these patients. Indeed, we showed that depletion of CD4 ϩ CD25 ϩ cells clearly increased the HBcAg-specific T-cell response in 17 patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection†‡

et al. 2005

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection is H epatitis B virus (HBV) is a common noncyto-pathic DNA virus. Infection with HBV in adults results frequently in a self-limiting, acute hepatitis, which confers protective immunity and causes no further disease. In 10% of infected adults, HBV leads to a chronic infection. Chronic HBV infection is an important risk factor for the development of cirrhosis and hepatocellular carcinoma. Worldwide, 350 million people suffer from chronic HBV infection, and approximately 1 million people die annually from HBV-related liver disease. 1,2 T helper 1 type cytokines such as interferon ␥ (IFN-␥) and interleukin 2 are involved in cell-mediated immunity and play a crucial role in the protection against intracellular pathogens, including HBV. 3 In patients with an acute self-limiting HBV infection, a multispecific CD4 ϩ and CD8 ϩ T-cell response with a type 1 cytokine profile is important for control of the infection. 4 These multispecific T-cell responses are maintained for decades after clinical recovery. 5 In contrast, patients with a chronic HBV infection lack such a vigorous multispecific response. These patients have a weak or undetectable virus-specific T-cell response. 4 The precise mechanism responsible for this T-cell hyporesponsiveness or tolerance is still unknown. One scenario that has not been explored in relation to chronic HBV infection is the potential role of host-mediated immunosuppressive mechanisms that might be activated in the face of persistent antigenic exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The effector cells suppressed by T reg are mainly CD4 ϩ T cells, because HBcAg has been described to induce predominantly a CD4 ϩ Tcell response. 27 Furthermore, when the isolated T reg were reconstituted to the T reg -depleted fraction, the proliferation and IFN-␥ production were suppressed in a dosedependent manner.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection†‡

et al. 2005

View full text Add to dashboard Cite

show abstract

“…We have shown that adoptive transfer of immunity to HBV, with T-cells reactive to HBcAg in bone marrow recipients, results in resolution of chronic HBV infection. 21 Immunotherapy with dendritic cells can induce efficient antiviral T-cells responses, 44 and a clinical application of virus-pulsed dendritic cells in HIV-infected patients was effective in inducing lasting Th1 responses with prolonged viral suppression. 45 Another approach, which deserves further investigations, is ex vivo expansion of autologous virusspecific T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…T-cell proliferative response to hepatitis B core antigen (HBcAg) was analyzed with fresh peripheral blood mononuclear cells (PBMC), as previously described. 21 Briefly, PBMC were isolated from heparinized blood by density gradient centrifugation and were cultured for 6 days in 96-well plates (2 ϫ 10 5 cells/ well) in RPMI-1640 with 10% (vol/vol) heatinactivated human AB serum (Gemini, Calabasas, CA) with and without HBcAg (1 g/mL American Research Products, Belmont, MA). Tetanus toxoid (0.5 g/mL, Connaught Laboratories, Ontario, Canada) and phytohemagglutinin (Sigma, Dorset, UK) were included as positive controls.…”

Section: Methodsmentioning

confidence: 99%

“…PBMC were cryopreserved during the study and used to determine the frequency of HBcAg-specific, IFN-␥-producing T-cells using an Elispot assay. 21 The PBMC samples from all time-points per patient were tested simultaneously. Briefly, nitrocellulose-bottom 96-well plates (Millipore, Bedford, MA) were coated overnight at 4°C with monoclonal antibody to IFN-␥ (anti-IFN-␥, Mabtech, Nacka, Sweden) at 10 g/mL in phosphatebuffered saline.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lamivudine Plus Interleukin-12 Combination Therapy in Chronic Hepatitis B: Antiviral and Immunological Activity *

et al. 2005

Self Cite

View full text Add to dashboard Cite

H epatitis B virus (HBV) is a noncytopathic DNAvirus, which can cause acute, self-limited hepatitis or chronic hepatitis, cirrhosis, and/or hepatocellular carcinoma. 1 The diversity of clinical outcomes after exposure to HBV is determined primarily by the host immune response. 2,3 The resolution of HBV infection after acute self-limited hepatitis is associated with strong CD4ϩ and CD8ϩ T-cell responses, with a type 1 cytokine profile. [4][5][6][7] In contrast to this strong antiviral T-cell reactivity, which persists in the convalescent phase after hepatitis B surface antigen (HBsAg) clearance, patients with chronic HBV infection have weak or undetectable T-cell reactivity to HBV, which is the dominant factor that permits an ongoing, high level of viral replication. A series of investigations of the mechanisms by which Tcells control HBV replication showed the major role of cytokine-mediated, intracellular inactivation of HBV that does not require cell death. 8 This noncytolytic antiviral effect, first demonstrated in an HBV transgenic mouse model and subsequently in other animals, is primarily mediated by interferon-gamma (IFN-␥). 9-11 A detailed analysis of HBV clearance during acute infection in chimpanzees showed that the disappearance of viral DNA from the liver coincides with IFN-␥ induction before the increase of serum alanine aminotransferase (ALT), in other words, without destruction of hepatocytes. 11

show abstract

Gastrointestinal and Hepatic Complications

Strasser¹,

McDonald²

2003

Thomas' Hematopoietic Cell Transplantation

View full text Add to dashboard Cite

Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen

Cited by 167 publications

References 35 publications

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection†‡

Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection†‡

Lamivudine Plus Interleukin-12 Combination Therapy in Chronic Hepatitis B: Antiviral and Immunological Activity *

Gastrointestinal and Hepatic Complications

Contact Info

Product

Resources

About