Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4(+) T cell responses

[Guest guest]

Vaccine. 2011 Mar 2. [Epub ahead of print]

Impaired hepatitis B vaccine responses during chronic hepatitis C infection:

Involvement of the PD-1 pathway in regulating CD4(+) T cell responses.

Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick

T, Yao ZQ.

Medical Service, Department of Veterans Affairs, H. Quillen VA Medical

Center, City, TN 37614, USA; Department of Internal Medicine, Division

of Infectious Diseases, H. Quillen College of Medicine, East Tennessee

State University, City, TN 37614, USA.

Abstract

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus

(HCV) infection is recommended, but responses to vaccination are blunted when

compared to uninfected populations. The mechanism for this failure of immune

response in HCV-infected subjects remains unknown but is thought to be a result

of lymphocyte dysfunction during chronic viral infection. We have recently

demonstrated that PD-1, a novel negative immunomodulator for T cell receptor

(TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic

HCV infection. In this report, we further investigated the role of the PD-1

pathway in regulation of CD4(+) T cell responses to HBV vaccination in

HCV-infected individuals. In a prospective HCV infected cohort, a poor response

rate to HBV vaccination as assayed by seroconversion was observed in

HCV-infected subjects (53%), while a high response rate was observed in healthy

or spontaneously HCV-resolved individuals (94%). CD4(+) T cell responses to ex

vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen

(HBsAg) were found to be lower in HBV vaccine non-responders compared to those

responders in HCV-infected individuals who had received a series of HBV

immunizations. PD-1 expression on CD4(+) T cells was detected at relatively

higher levels in these HBV vaccine non-responders than those who responded, and

this was inversely associated with the cell activation status. Importantly,

blocking the PD-1 pathway improved T cell activation and proliferation in

response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine

non-responders. These results suggest that PD-1 signaling may be involved in

impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV

infection, and raise the possibility that blocking this negative signaling

pathway might improve success rates of immunization in the setting of chronic

viral infection.Copyright © 2011. Published by Elsevier Ltd.

PMID: 21376795 [PubMed - as supplied by publisher]

[Guest guest]

Vaccine. 2011 Mar 2. [Epub ahead of print]

Impaired hepatitis B vaccine responses during chronic hepatitis C infection:

Involvement of the PD-1 pathway in regulating CD4(+) T cell responses.

Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick

T, Yao ZQ.

Medical Service, Department of Veterans Affairs, H. Quillen VA Medical

Center, City, TN 37614, USA; Department of Internal Medicine, Division

of Infectious Diseases, H. Quillen College of Medicine, East Tennessee

State University, City, TN 37614, USA.

Abstract

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus

(HCV) infection is recommended, but responses to vaccination are blunted when

compared to uninfected populations. The mechanism for this failure of immune

response in HCV-infected subjects remains unknown but is thought to be a result

of lymphocyte dysfunction during chronic viral infection. We have recently

demonstrated that PD-1, a novel negative immunomodulator for T cell receptor

(TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic

HCV infection. In this report, we further investigated the role of the PD-1

pathway in regulation of CD4(+) T cell responses to HBV vaccination in

HCV-infected individuals. In a prospective HCV infected cohort, a poor response

rate to HBV vaccination as assayed by seroconversion was observed in

HCV-infected subjects (53%), while a high response rate was observed in healthy

or spontaneously HCV-resolved individuals (94%). CD4(+) T cell responses to ex

vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen

(HBsAg) were found to be lower in HBV vaccine non-responders compared to those

responders in HCV-infected individuals who had received a series of HBV

immunizations. PD-1 expression on CD4(+) T cells was detected at relatively

higher levels in these HBV vaccine non-responders than those who responded, and

this was inversely associated with the cell activation status. Importantly,

blocking the PD-1 pathway improved T cell activation and proliferation in

response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine

non-responders. These results suggest that PD-1 signaling may be involved in

impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV

infection, and raise the possibility that blocking this negative signaling

pathway might improve success rates of immunization in the setting of chronic

viral infection.Copyright © 2011. Published by Elsevier Ltd.

PMID: 21376795 [PubMed - as supplied by publisher]

[Guest guest]

Vaccine. 2011 Mar 2. [Epub ahead of print]

Impaired hepatitis B vaccine responses during chronic hepatitis C infection:

Involvement of the PD-1 pathway in regulating CD4(+) T cell responses.

Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick

T, Yao ZQ.

Medical Service, Department of Veterans Affairs, H. Quillen VA Medical

Center, City, TN 37614, USA; Department of Internal Medicine, Division

of Infectious Diseases, H. Quillen College of Medicine, East Tennessee

State University, City, TN 37614, USA.

Abstract

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus

(HCV) infection is recommended, but responses to vaccination are blunted when

compared to uninfected populations. The mechanism for this failure of immune

response in HCV-infected subjects remains unknown but is thought to be a result

of lymphocyte dysfunction during chronic viral infection. We have recently

demonstrated that PD-1, a novel negative immunomodulator for T cell receptor

(TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic

HCV infection. In this report, we further investigated the role of the PD-1

pathway in regulation of CD4(+) T cell responses to HBV vaccination in

HCV-infected individuals. In a prospective HCV infected cohort, a poor response

rate to HBV vaccination as assayed by seroconversion was observed in

HCV-infected subjects (53%), while a high response rate was observed in healthy

or spontaneously HCV-resolved individuals (94%). CD4(+) T cell responses to ex

vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen

(HBsAg) were found to be lower in HBV vaccine non-responders compared to those

responders in HCV-infected individuals who had received a series of HBV

immunizations. PD-1 expression on CD4(+) T cells was detected at relatively

higher levels in these HBV vaccine non-responders than those who responded, and

this was inversely associated with the cell activation status. Importantly,

blocking the PD-1 pathway improved T cell activation and proliferation in

response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine

non-responders. These results suggest that PD-1 signaling may be involved in

impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV

infection, and raise the possibility that blocking this negative signaling

pathway might improve success rates of immunization in the setting of chronic

viral infection.Copyright © 2011. Published by Elsevier Ltd.

PMID: 21376795 [PubMed - as supplied by publisher]

[Guest guest]

Vaccine. 2011 Mar 2. [Epub ahead of print]

Impaired hepatitis B vaccine responses during chronic hepatitis C infection:

Involvement of the PD-1 pathway in regulating CD4(+) T cell responses.

Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick

T, Yao ZQ.

Medical Service, Department of Veterans Affairs, H. Quillen VA Medical

Center, City, TN 37614, USA; Department of Internal Medicine, Division

of Infectious Diseases, H. Quillen College of Medicine, East Tennessee

State University, City, TN 37614, USA.

Abstract

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus

(HCV) infection is recommended, but responses to vaccination are blunted when

compared to uninfected populations. The mechanism for this failure of immune

response in HCV-infected subjects remains unknown but is thought to be a result

of lymphocyte dysfunction during chronic viral infection. We have recently

demonstrated that PD-1, a novel negative immunomodulator for T cell receptor

(TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic

HCV infection. In this report, we further investigated the role of the PD-1

pathway in regulation of CD4(+) T cell responses to HBV vaccination in

HCV-infected individuals. In a prospective HCV infected cohort, a poor response

rate to HBV vaccination as assayed by seroconversion was observed in

HCV-infected subjects (53%), while a high response rate was observed in healthy

or spontaneously HCV-resolved individuals (94%). CD4(+) T cell responses to ex

vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen

(HBsAg) were found to be lower in HBV vaccine non-responders compared to those

responders in HCV-infected individuals who had received a series of HBV

immunizations. PD-1 expression on CD4(+) T cells was detected at relatively

higher levels in these HBV vaccine non-responders than those who responded, and

this was inversely associated with the cell activation status. Importantly,

blocking the PD-1 pathway improved T cell activation and proliferation in

response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine

non-responders. These results suggest that PD-1 signaling may be involved in

impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV

infection, and raise the possibility that blocking this negative signaling

pathway might improve success rates of immunization in the setting of chronic

viral infection.Copyright © 2011. Published by Elsevier Ltd.

PMID: 21376795 [PubMed - as supplied by publisher]