Virus-specific CD4+ T cell responses in chronic HCV infection in blood and liver identified by antigen-specific upregulation of CD154.

[Guest guest]

J Hepatol. 2010 Mar 26. [Epub ahead of print]

Virus-specific CD4+ T cell responses in chronic HCV infection in blood and liver

identified by antigen-specific upregulation of CD154.

Mueller M, Spangenberg HC, Kersting N, Altay T, Blum HE, Klenerman P, Thimme R,

Semmo N.

Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.

Abstract

BACKGROUND & AIMS: Virus-specific CD4+ T cells play a major role in hepatitis C

virus (HCV) infection. Viral clearance is associated with vigorous and

multispecific CD4+ T cell responses, while chronic infection has been shown to

be associated with weak or absent T cell responses. Most of these studies,

however, have used functional assays to analyse virus-specific CD4+ T cell

responses. Therefore, the important question of whether virus-specific CD4+ T

cells are completely absent or primarily impaired in specific effector functions

during chronic infection has yet to be analysed in detail. METHODS: To address

this issue, a novel assay where CD4+ T cell frequencies can be determined by de

novo CD154 (CD40 ligand) expression in response to HCV antigens was used in a

cohort of chronically infected HCV patients and patients who spontaneously

resolved HCV infection. These responses were compared with functional assays,

such as the IFN-gamma ELISpot and flow cytometry-based proliferative assays.

RESULTS: Our results reveal that using the CD154 assay, virus-specific CD4+ T

cells are readily detectable during chronic HCV infection albeit at a lower

frequency when compared to patients who spontaneously resolved the infection.

Importantly, no CD4+ T cell responses were detectable from these patients when

using functional assays. Finally, these cell populations were enriched in the

intrahepatic compartment. CONCLUSIONS: Our findings suggest that HCV-specific

CD4+ T cell responses are readily detectable in chronic HCV infection and

enriched in the infected liver. European Association for the

Study of the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 20416967 [PubMed - as supplied by publisher]

[Guest guest]

J Hepatol. 2010 Mar 26. [Epub ahead of print]

Virus-specific CD4+ T cell responses in chronic HCV infection in blood and liver

identified by antigen-specific upregulation of CD154.

Mueller M, Spangenberg HC, Kersting N, Altay T, Blum HE, Klenerman P, Thimme R,

Semmo N.

Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.

Abstract

BACKGROUND & AIMS: Virus-specific CD4+ T cells play a major role in hepatitis C

virus (HCV) infection. Viral clearance is associated with vigorous and

multispecific CD4+ T cell responses, while chronic infection has been shown to

be associated with weak or absent T cell responses. Most of these studies,

however, have used functional assays to analyse virus-specific CD4+ T cell

responses. Therefore, the important question of whether virus-specific CD4+ T

cells are completely absent or primarily impaired in specific effector functions

during chronic infection has yet to be analysed in detail. METHODS: To address

this issue, a novel assay where CD4+ T cell frequencies can be determined by de

novo CD154 (CD40 ligand) expression in response to HCV antigens was used in a

cohort of chronically infected HCV patients and patients who spontaneously

resolved HCV infection. These responses were compared with functional assays,

such as the IFN-gamma ELISpot and flow cytometry-based proliferative assays.

RESULTS: Our results reveal that using the CD154 assay, virus-specific CD4+ T

cells are readily detectable during chronic HCV infection albeit at a lower

frequency when compared to patients who spontaneously resolved the infection.

Importantly, no CD4+ T cell responses were detectable from these patients when

using functional assays. Finally, these cell populations were enriched in the

intrahepatic compartment. CONCLUSIONS: Our findings suggest that HCV-specific

CD4+ T cell responses are readily detectable in chronic HCV infection and

enriched in the infected liver. European Association for the

Study of the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 20416967 [PubMed - as supplied by publisher]