Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 2Date:2 December 2012
Reviewer: Robert Thimme
Reviewer's report:
In this well performed an clinical relevant study, Peter et al performed a
comprehensive phenotypical and functional analysis of T cell function, phenotype
and cytokine profiles in patients with liver cirrhosis and patients with liver
cirrhosis and inflammation (as indicated by CRP levels). Especially in patients
with liver cirrhosis and inflammation, they found higher levels of IL-10, an
expansion of CD14+ monocytes with a low HLA-DR expression and an increased
expression and an increased proportion of CD25+ CD4+ and CD8+ T cells. While
in these patients, TNFa production of CD4+ and CD8+ T cells was reduced after
stimulation with SEB, this was not significant when comparing the overall group
of cirrhotic patients and healthy controls. Also, no significant difference in the
antigen-specific T cell response against Ebstein Barr virus was observed.
However, patients without any virus-specific T cell response showed higher IL-10
levels. In sum, this study is well performed with adequate controls and comes to
clear conclusions.
I have the following comments:
Major:
1. In Figures 2, 3 and 4 original data should be displayed to allow the reader/
reviewer to judge the data quality.
2. The increase expression of CD25+ on CD4+ T cells suggests that these cells
may indeed be regulatory T cells as the authors discuss themselves. Why have
they not stained for Foxp3 or have performed suppression assays? This should
be stated.
3. The possible source of elevated IL-10 should be discussed in more detail.
4. HLA-Dr is also an activating marker. Its down-regulation might suggest that
cells are less activated during inflammation in cirrhosis. Why have the authors
not used other activation markers such as CD69 or CD38 to address activation?
Minor:
1. In the abstract, the authors state three pre-defined groups with defining those.
That should be done more clearly.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interest
Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 2Date:2 December 2012
Reviewer: Robert Thimme
Reviewer's report:
In this well performed an clinical relevant study, Peter et al performed a
comprehensive phenotypical and functional analysis of T cell function, phenotype
and cytokine profiles in patients with liver cirrhosis and patients with liver
cirrhosis and inflammation (as indicated by CRP levels). Especially in patients
with liver cirrhosis and inflammation, they found higher levels of IL-10, an
expansion of CD14+ monocytes with a low HLA-DR expression and an increased
expression and an increased proportion of CD25+ CD4+ and CD8+ T cells. While
in these patients, TNFa production of CD4+ and CD8+ T cells was reduced after
stimulation with SEB, this was not significant when comparing the overall group
of cirrhotic patients and healthy controls. Also, no significant difference in the
antigen-specific T cell response against Ebstein Barr virus was observed.
However, patients without any virus-specific T cell response showed higher IL-10
levels. In sum, this study is well performed with adequate controls and comes to
clear conclusions.
I have the following comments:
Major:
1. In Figures 2, 3 and 4 original data should be displayed to allow the reader/
reviewer to judge the data quality.
2. The increase expression of CD25+ on CD4+ T cells suggests that these cells
may indeed be regulatory T cells as the authors discuss themselves. Why have
they not stained for Foxp3 or have performed suppression assays? This should
be stated.
3. The possible source of elevated IL-10 should be discussed in more detail.
4. HLA-Dr is also an activating marker. Its down-regulation might suggest that
cells are less activated during inflammation in cirrhosis. Why have the authors
not used other activation markers such as CD69 or CD38 to address activation?
Minor:
1. In the abstract, the authors state three pre-defined groups with defining those.
That should be done more clearly.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interest
Please review this paper.
user
Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 2Date:2 December 2012
Reviewer: Robert Thimme
Reviewer's report:
In this well performed an clinical relevant study, Peter et al performed a
comprehensive phenotypical and functional analysis of T cell function, phenotype
and cytokine profiles in patients with liver cirrhosis and patients with liver
cirrhosis and inflammation (as indicated by CRP levels). Especially in patients
with liver cirrhosis and inflammation, they found higher levels of IL-10, an
expansion of CD14+ monocytes with a low HLA-DR expression and an increased
expression and an increased proportion of CD25+ CD4+ and CD8+ T cells. While
in these patients, TNFa production of CD4+ and CD8+ T cells was reduced after
stimulation with SEB, this was not significant when comparing the overall group
of cirrhotic patients and healthy controls. Also, no significant difference in the
antigen-specific T cell response against Ebstein Barr virus was observed.
However, patients without any virus-specific T cell response showed higher IL-10
levels. In sum, this study is well performed with adequate controls and comes to
clear conclusions.
I have the following comments:
Major:
1. In Figures 2, 3 and 4 original data should be displayed to allow the reader/
reviewer to judge the data quality.
2. The increase expression of CD25+ on CD4+ T cells suggests that these cells
may indeed be regulatory T cells as the authors discuss themselves. Why have
they not stained for Foxp3 or have performed suppression assays? This should
be stated.
3. The possible source of elevated IL-10 should be discussed in more detail.
4. HLA-Dr is also an activating marker. Its down-regulation might suggest that
cells are less activated during inflammation in cirrhosis. Why have the authors
not used other activation markers such as CD69 or CD38 to address activation?
Minor:
1. In the abstract, the authors state three pre-defined groups with defining those.
That should be done more clearly.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interest
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