Upregulation of CXCR3 expression on CD8+ T cells due to the pervasive influence of chronic hepatitis B and C virus infection

Niet, A. de; Bruijne, Joep de; Plat-Sinnige, Marjan J. Tempelmans; Takkenberg, R. Bart; Lier, R. A. W. Van; Reesink, H. W.; Leeuwen, Ester M. M. van

doi:10.1016/j.humimm.2013.04.017

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…This suggests that continued PEG‐IFN therapy in poor responders further elevates the nonspecific inflammatory response, which may be related to the persistence of HBsAg in the uncured group. Consistent with the results of previous studies, the increase in serum chemokine levels and the proportion of CXCR3 + CTL were closely associated with persistent viral infection, and the mechanisms underlying this need to be further elucidated 24,25 …”

Section: Discussionsupporting

confidence: 80%

“…Consistent with the results of previous studies, the increase in serum chemokine levels and the proportion of CXCR3 + CTL were closely associated with persistent viral infection, and the mechanisms underlying this need to be further elucidated. 24,25 Furthermore, our results showed that IFN-α could promote the polarization of IFN-γ + Th1 cells by downregulating HDAC6 expression level of T cells, suggesting that IFN-α has a regulatory effect on the polarization of Th1 cells. This finding, to a certain extent, reveals the immune-regulatory mechanism by which IFN-α promotes HBsAg loss.…”

Section: Discussionmentioning

confidence: 60%

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Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Wu,

Deng,

Feng

et al. 2024

Journal of Medical Virology

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The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon‐α (PEG‐IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG‐IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP‐1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN‐γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell‐associated chemokines (C‐X‐C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN‐γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue‐resident memory T cells with increased ALT levels. IFN‐γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 60%

Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Wu,

Deng,

Feng

et al. 2024

Journal of Medical Virology

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“…There are no studies on the latent function of peritumoral imflammatory adhesions; however, the association between CXCR3 and inflammation is clear. Dysregulation of CXCR3 expression has been found in viral infections ( 29 ), autoimmune diseases ( 30 ), allergy and asthma. To the best of our knowledge, the present study is the first to provide supportive evidence for the hypothesis that CRC prognosis is associated with the presence of inflammatory adhesions and CXCR3 expression.…”

Section: Discussionmentioning

confidence: 99%

CXCL10/CXCR3 overexpression as a biomarker of poor prognosis in patients with stage II colorectal cancer

Bai

Chen

2015

Molecular and Clinical Oncology

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The CXCL10/CXCR3 axis of inflammatory mediators is one of the most important groups of chemokine axes, which has been proven to be a lymphocyte-associated metastasis mediator in several tumors. The term inflammatory adhesions refers to tumors found to be attached to the surrouding tissues during surgery, although no cancer cell infiltration is later identified on pathological examination. The aim of the present study was to investigate the clinical characteristics of stage II colorectal cancer (CRC) and determine the correlation between the CXCL10/CXCR3 axis, inflammatory adhesions and prognosis. Clinicohistopathological data were collected from 401 CRC patients who had undergone R0 resection. Statistical analysis was performed with SPSS 17.0 software. Immunohistochemistry (IHC) was applied to measure the expression of CXCL10 and CXCR3 in 71 recurrent CRC patients, 72 non-recurrent CRC patients and 10 samples from normal peritumoral tissues, all retrieved from the Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Inflammatory adhesions, tumor location and size and the number of high-risk factors for reccurrence were more significantly associated with overall survival (OS) rather than disease-free survival in all the patients as determined by the log-rank and Cox's regression hazard analysis. Further analysis demonstrated that only the presence of inflammatory adhesions (P=0.025) was associated with the OS of recurrent patients. Patients with recurrence exhibited higher CXCR3 (P<0.001) and CXCL10 (P<0.001) expression compared with non-recurrent patients, as determined by IHC. The correlation between clinicopathological variables, CXCL10/CXCR3 expression and survival was also analyzed: Inflammatory adhesions and general tumor type (ulcerated vs. elevated) exhibited a significant correlation with CXCR3; however, the expression of CXCL10 was not significantly correlated with tumor location, histological type, size, gender, or preoperative carcinoembryonic antigen and hemoglobin levels. Furthermore, patients exhibiting a high expression of CXCR3 presented with a higher risk of relapse; among those, patients with inflammatory adhesions always exhibited worse survival. However, no such association was identified for CXCL10 expression. In conclusion, CXCR3 expression may be used as a prognostic marker and may contribute to the prediction of clinical outcome in stage II CRC patients.

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“…After an acute infection, the memory CD8 + T cell population evolves progressively over time into sub-populations that are enriched with cells with higher proliferative capacity, greater longevity, and with slight alterations during latent, chronic, and persistent phases of infections. 149,[167][168][169] How effector CD8 + T cell differentiation is balanced to permit the formation of effector cell properties in the MPECs and yet still prevents the MPECs from acquiring a terminal SLECs state is still controversial. More so, it is also unclear whether naïve (N) and effector (E) CD8 + T cells specific to symptomatic vs. asymptomatic epitopes follow a different path of development into memory (M) cells (i.e., designated in this review as symptomatic vs. asymptomatic N > > > E > > > M transitions).…”

Section: Models For Memory Cd8 + T Cells Development Within Symptomatmentioning

confidence: 99%

Asymptomatic memory CD8⁺T cells

Khan

Srivastava

Lopes

et al. 2014

Human Vaccines & Immunotherapeutics

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Generation and maintenance of high quantity and quality memory CD8(+) T cells determine the level of protection from viral, bacterial, and parasitic re-infections, and hence constitutes a primary goal for T cell epitope-based human vaccines and immunotherapeutics. Phenotypically and functionally characterizing memory CD8(+) T cells that provide protection against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections, which cause blinding ocular herpes, genital herpes, and oro-facial herpes, is critical for better vaccine design. We have recently categorized 2 new major sub-populations of memory symptomatic and asymptomatic CD8(+) T cells based on their phenotype, protective vs. pathogenic function, and anatomical locations. In this report we are discussing a new direction in developing T cell-based human herpes vaccines and immunotherapeutics based on the emerging new concept of "symptomatic and asymptomatic memory CD8(+) T cells."

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Upregulation of CXCR3 expression on CD8+ T cells due to the pervasive influence of chronic hepatitis B and C virus infection

Cited by 7 publications

References 33 publications

Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

CXCL10/CXCR3 overexpression as a biomarker of poor prognosis in patients with stage II colorectal cancer

Asymptomatic memory CD8⁺T cells

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Upregulation of CXCR3 expression on CD8+ T cells due to the pervasive influence of chronic hepatitis B and C virus infection

Cited by 7 publications

References 33 publications

Interferon‐γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Interferon‐γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

CXCL10/CXCR3 overexpression as a biomarker of poor prognosis in patients with stage II colorectal cancer

Asymptomatic memory CD8+T cells

Contact Info

Product

Resources

About

Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Interferon‐γ⁺ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization

Asymptomatic memory CD8⁺T cells