Dataset Information

CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells associate with unfavorable outcome in patients with chronic HBV infection.

ABSTRACT:

Background

A major barrier to achieving a favorable outcome of chronic HBV infection is a dysregulated HBV-specific immune response resulting from immunosuppressive features of FOXP3⁺ T cells. A better definition of FOXP3⁺ T cells is essential for improving the prognosis of HBV infection. We aimed to investigate the role of CD4⁺CXCR5^-FOXP3⁺ T cells with CTLA4 expression in patients with chronic HBV infection.

Methods

Treatment-naïve chronic HBV-infected patients, HBV-related hepatic failure, and a longitudinal cohort of chronic hepatitis B (CHB) patients with nucleos(t)ide analogue treatment were enrolled for analysis of CD4⁺CXCR5^-FOXP3⁺ T cell responses by flow cytometry and single-cell RNA sequencing (scRNA-seq).

Results

ScRNA-seq revealed that circulating CD4⁺CXCR5^-FOXP3⁺ T cells presented distinct inhibitory features compared to spleen tissue. Meanwhile, patients with treatment-naïve chronic HBV infection or with HBV-related hepatic failure showed an upregulation of immune-suppressive features (PD-1, CTLA4, GITR) on CD4⁺CXCR5^-FOXP3⁺T cells; in vitro analysis found HBeAg and HBcAg stimulation induced elevated levels of inhibitory molecules. Notably, the frequency of CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells was positively correlated with HBV DNA levels, and longitudinal analysis demonstrated a high frequency of this subset at 12 weeks of antiviral treatment predicted unfavorable outcome in CHB patients.

Conclusions

CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells are related to unfavorable outcomes in HBV-infected patients; these data indicated that alleviating CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells may improve the prognosis of HBV infection.

SUBMITTER: Wen C

PROVIDER: S-EPMC9835316 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

CTLA4<sup>+</sup>CD4<sup>+</sup>CXCR5<sup>-</sup>FOXP3<sup>+</sup> T cells associate with unfavorable outcome in patients with chronic HBV infection.

Wen Chunhua C Dong Zheyu Z Wang Yiyue Y Ye Guofu G Ma Yanchen Y Yi Xuan X Zhou Yang Y Li Xiaoyi X Zheng Xinchun X Hou Jinlin J Li Yongyin Y Tang Libo L

BMC immunology 20230112 1

<h4>Background</h4>A major barrier to achieving a favorable outcome of chronic HBV infection is a dysregulated HBV-specific immune response resulting from immunosuppressive features of FOXP3<sup>+</sup> T cells. A better definition of FOXP3<sup>+</sup> T cells is essential for improving the prognosis of HBV infection. We aimed to investigate the role of CD4<sup>+</sup>CXCR5<sup>-</sup>FOXP3<sup>+</sup> T cells with CTLA4 expression in patients with chronic HBV infection.<h4>Methods</h4>Treatment ...[more]

PMID: 36635631

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Project description:BackgroundPrognostic biomarkers of treatment response to distinct biologic disease-modifying anti-rheumatic drugs (b-DMARDs) are still lacking within the management of rheumatoid arthritis (RA).MethodsThirty-four b-DMARDs naive RA patients, divided by disease duration into early (cohort 1) and long standing (cohort 2), received CTLA4-Ig. At study entry, and every 3 months for 1 year, each patient underwent peripheral blood (PB)-derived CD4pos cell subpopulation assessment by flow cytometry, STAT3 and STAT5 expression by RT-PCR and IL-6, IL-12p70, TGFβ, and IL-10 serum levels by ELISA. The DAS and CDAI remission was assessed at 6 and 12 months.ResultsDAS- and CDAI-defined remission within 12 months was achieved by 16 (47.1%) and 8 (23.5%) RA patients, respectively. Considering the whole RA cohort, CTLA4-Ig induced a significant decrease of IL-6 serum levels from baseline to 6 and 12 months, as well as of PB CD4posCD25posFoxP3pos cells at 6 and 12 months, and of CD4posIL17pos cells after 12 months. PB CD4pos cells of RA patients showed higher STAT3 and STAT5 expression than healthy controls, which remained unchanged within 12 months of treatment. At study entry, RA patients achieving DAS remission had significantly lower IL-6 serum levels than RA patients not achieving this outcome. In particular, having baseline IL-6 serum levels ≤ 8.4 pg/ml, significantly identified naïve to b-DMARDs RA patients more likely to achieve DAS-remission under CTLA4-Ig at 6 months (66.7%) compared to RA patients with baseline IL-6 serum levels > 8.4 pg/ml [15.4%, OR (95%Cis) 11.00 (1.75-55.82)]. Moreover, having CD4posCD25posFoxP3pos cells rate ≥ 6.0% significantly identifies naïve to b-DMARDs early RA patients more likely to achieve DAS remission at 6 months (83.3%) compared to RA patients with baseline CD4posCD25posFoxP3pos cells < 6.0% [16.7%, OR (95% Cis) 25.00 (1.00-336.81)].ConclusionsBaseline IL-6 serum levels and peripheral blood-derived CD4pos subpopulations are putative novel prognostic biomarkers of CTLA4-Ig response in RA patients.

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Dataset Information

CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells associate with unfavorable outcome in patients with chronic HBV infection.

Background

Methods

Results

Conclusions

Publications

CTLA4<sup>+</sup>CD4<sup>+</sup>CXCR5<sup>-</sup>FOXP3<sup>+</sup> T cells associate with unfavorable outcome in patients with chronic HBV infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

CTLA4+CD4+CXCR5-FOXP3+ T cells associate with unfavorable outcome in patients with chronic HBV infection.

Background

Methods

Results

Conclusions

Publications

CTLA4<sup>+</sup>CD4<sup>+</sup>CXCR5<sup>-</sup>FOXP3<sup>+</sup> T cells associate with unfavorable outcome in patients with chronic HBV infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CTLA4⁺CD4⁺CXCR5^-FOXP3⁺ T cells associate with unfavorable outcome in patients with chronic HBV infection.