Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates With the Outcome of A

[Guest guest]

Gastroenterology. 2008 Mar 22 [Epub ahead of print]

Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates

With the Outcome of Acute Hepatitis B.

Zhang Z, Zhang JY, Wherry EJ, Jin B, Xu B, Zou ZS, Zhang SY, Li BS, Wang HF, Wu

H, Fu YX, Wang FS.

Research Center for Biological Therapy, Beijing, China.

BACKGROUND & AIMS: Recent studies have shown that programmed death 1 (PD-1)

expression can impair virus-specific CD8 T-cell responses during chronic viral

infection, including hepatitis B virus (HBV). This study aimed to characterize

the PD-1 expression during acute hepatitis B (AHB) and further address whether

and how the PD-1-mediated pathway balances antiviral immunity versus

immunopathology, possibly contributing to disease progression. METHODS:

Peripheral and intrahepatic PD-1 expression was investigated longitudinally in

23 human HLA-A2-positive patients with acute hepatitis B. Four patients with

HBV-related acute liver failure, 13 patients with chronic hepatitis B, and 9

healthy individuals were enrolled as controls. Flow cytometric,

immunohistochemical, and immunofunctional assays were performed to analyze the

impact of PD-1 expression. RESULTS: PD-1 expression was significantly

up-regulated on HBV-specific CD8 T cells in the early phase of acute HBV

infection, and successful viral clearance correlated with a subsequent decrease

in PD-1 expression. Blocking the PD-1-mediated pathway in vitro enhanced

HBV-specific CD8 T-cell proliferation and inflammatory cytokine production,

while reducing interleukin-10 production and apoptosis, confirming the essential

role of PD-1 in tempering the T-cell response during the acute phase of

infection. In contrast, delayed PD-1 expression on HBV-specific CD8 T cells was

associated with acute liver failure. CONCLUSIONS: PD-1 up-regulation may

efficiently mitigate pathogenic CD8 T-cell responses and liver damage,

correlating with disease progression of acute HBV infection. This study

therefore shows how this negative signaling pathway functions in such early HBV

infection, which will be important for better clinical management, prognosis,

and new HBV treatments.

PMID: 18455515 [PubMed - as supplied by publisher]

_________________________________________________________________

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Gastroenterology. 2008 Mar 22 [Epub ahead of print]

Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates

With the Outcome of Acute Hepatitis B.

Zhang Z, Zhang JY, Wherry EJ, Jin B, Xu B, Zou ZS, Zhang SY, Li BS, Wang HF, Wu

H, Fu YX, Wang FS.

Research Center for Biological Therapy, Beijing, China.

BACKGROUND & AIMS: Recent studies have shown that programmed death 1 (PD-1)

expression can impair virus-specific CD8 T-cell responses during chronic viral

infection, including hepatitis B virus (HBV). This study aimed to characterize

the PD-1 expression during acute hepatitis B (AHB) and further address whether

and how the PD-1-mediated pathway balances antiviral immunity versus

immunopathology, possibly contributing to disease progression. METHODS:

Peripheral and intrahepatic PD-1 expression was investigated longitudinally in

23 human HLA-A2-positive patients with acute hepatitis B. Four patients with

HBV-related acute liver failure, 13 patients with chronic hepatitis B, and 9

healthy individuals were enrolled as controls. Flow cytometric,

immunohistochemical, and immunofunctional assays were performed to analyze the

impact of PD-1 expression. RESULTS: PD-1 expression was significantly

up-regulated on HBV-specific CD8 T cells in the early phase of acute HBV

infection, and successful viral clearance correlated with a subsequent decrease

in PD-1 expression. Blocking the PD-1-mediated pathway in vitro enhanced

HBV-specific CD8 T-cell proliferation and inflammatory cytokine production,

while reducing interleukin-10 production and apoptosis, confirming the essential

role of PD-1 in tempering the T-cell response during the acute phase of

infection. In contrast, delayed PD-1 expression on HBV-specific CD8 T cells was

associated with acute liver failure. CONCLUSIONS: PD-1 up-regulation may

efficiently mitigate pathogenic CD8 T-cell responses and liver damage,

correlating with disease progression of acute HBV infection. This study

therefore shows how this negative signaling pathway functions in such early HBV

infection, which will be important for better clinical management, prognosis,

and new HBV treatments.

PMID: 18455515 [PubMed - as supplied by publisher]

_________________________________________________________________

Windows Live SkyDrive lets you share files with faraway friends.

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rive_052008

[Guest guest]

Gastroenterology. 2008 Mar 22 [Epub ahead of print]

Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates

With the Outcome of Acute Hepatitis B.

Zhang Z, Zhang JY, Wherry EJ, Jin B, Xu B, Zou ZS, Zhang SY, Li BS, Wang HF, Wu

H, Fu YX, Wang FS.

Research Center for Biological Therapy, Beijing, China.

BACKGROUND & AIMS: Recent studies have shown that programmed death 1 (PD-1)

expression can impair virus-specific CD8 T-cell responses during chronic viral

infection, including hepatitis B virus (HBV). This study aimed to characterize

the PD-1 expression during acute hepatitis B (AHB) and further address whether

and how the PD-1-mediated pathway balances antiviral immunity versus

immunopathology, possibly contributing to disease progression. METHODS:

Peripheral and intrahepatic PD-1 expression was investigated longitudinally in

23 human HLA-A2-positive patients with acute hepatitis B. Four patients with

HBV-related acute liver failure, 13 patients with chronic hepatitis B, and 9

healthy individuals were enrolled as controls. Flow cytometric,

immunohistochemical, and immunofunctional assays were performed to analyze the

impact of PD-1 expression. RESULTS: PD-1 expression was significantly

up-regulated on HBV-specific CD8 T cells in the early phase of acute HBV

infection, and successful viral clearance correlated with a subsequent decrease

in PD-1 expression. Blocking the PD-1-mediated pathway in vitro enhanced

HBV-specific CD8 T-cell proliferation and inflammatory cytokine production,

while reducing interleukin-10 production and apoptosis, confirming the essential

role of PD-1 in tempering the T-cell response during the acute phase of

infection. In contrast, delayed PD-1 expression on HBV-specific CD8 T cells was

associated with acute liver failure. CONCLUSIONS: PD-1 up-regulation may

efficiently mitigate pathogenic CD8 T-cell responses and liver damage,

correlating with disease progression of acute HBV infection. This study

therefore shows how this negative signaling pathway functions in such early HBV

infection, which will be important for better clinical management, prognosis,

and new HBV treatments.

PMID: 18455515 [PubMed - as supplied by publisher]

_________________________________________________________________

Windows Live SkyDrive lets you share files with faraway friends.

http://www.windowslive.com/skydrive/overview.html?ocid=TXT_TAGLM_WL_Refresh_skyd\

rive_052008

[Guest guest]

Gastroenterology. 2008 Mar 22 [Epub ahead of print]

Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates

With the Outcome of Acute Hepatitis B.

Zhang Z, Zhang JY, Wherry EJ, Jin B, Xu B, Zou ZS, Zhang SY, Li BS, Wang HF, Wu

H, Fu YX, Wang FS.

Research Center for Biological Therapy, Beijing, China.

BACKGROUND & AIMS: Recent studies have shown that programmed death 1 (PD-1)

expression can impair virus-specific CD8 T-cell responses during chronic viral

infection, including hepatitis B virus (HBV). This study aimed to characterize

the PD-1 expression during acute hepatitis B (AHB) and further address whether

and how the PD-1-mediated pathway balances antiviral immunity versus

immunopathology, possibly contributing to disease progression. METHODS:

Peripheral and intrahepatic PD-1 expression was investigated longitudinally in

23 human HLA-A2-positive patients with acute hepatitis B. Four patients with

HBV-related acute liver failure, 13 patients with chronic hepatitis B, and 9

healthy individuals were enrolled as controls. Flow cytometric,

immunohistochemical, and immunofunctional assays were performed to analyze the

impact of PD-1 expression. RESULTS: PD-1 expression was significantly

up-regulated on HBV-specific CD8 T cells in the early phase of acute HBV

infection, and successful viral clearance correlated with a subsequent decrease

in PD-1 expression. Blocking the PD-1-mediated pathway in vitro enhanced

HBV-specific CD8 T-cell proliferation and inflammatory cytokine production,

while reducing interleukin-10 production and apoptosis, confirming the essential

role of PD-1 in tempering the T-cell response during the acute phase of

infection. In contrast, delayed PD-1 expression on HBV-specific CD8 T cells was

associated with acute liver failure. CONCLUSIONS: PD-1 up-regulation may

efficiently mitigate pathogenic CD8 T-cell responses and liver damage,

correlating with disease progression of acute HBV infection. This study

therefore shows how this negative signaling pathway functions in such early HBV

infection, which will be important for better clinical management, prognosis,

and new HBV treatments.

PMID: 18455515 [PubMed - as supplied by publisher]

_________________________________________________________________

Windows Live SkyDrive lets you share files with faraway friends.

http://www.windowslive.com/skydrive/overview.html?ocid=TXT_TAGLM_WL_Refresh_skyd\

rive_052008