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CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.

Tang ZS, Hao YH, Zhang EJ, Xu CL, Zhou Y, Zheng X, Yang DL - Mol Med Rep (2016)

Bottom Line: The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals.A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml.A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD‑1 blockade on the receptor expression profiles and the levels of interferon (IFN)‑γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T‑box 21 (T‑bet) and GATA binding protein 3 (GATA‑3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD‑1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T‑bet/GATA‑3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid monitoring of changes in T cell function during CHB treatment. Furthermore, PD‑1 blockade has a therapeutic potential that may be enhanced by modulating the expression of co-stimulatory and -inhibitory receptors of the CD28 family.

No MeSH data available.


Related in: MedlinePlus

Anti-PD-L1 treatment and expression of CD28 family receptors. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients (n=22) were isolated and cultured in the presence of anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days. Cells were treated with anti-PD-L1 antibody or isotype antibody at a concentration of 5 µg/ml. (A) Representative flow cytometric dot plots of CD28 family receptors on CD4+ T cells with PD-1 blockade or isotype antibody treatment from a patient with CHB. (B) Expression of the receptors with PD-1 blockade or isotype antibody treatment. The fold-change of a single receptor was calculated by percentage following PD-1 blockade/before blockade. (C) Cumulative data showing fold-changes of PD-1 in CD4+ T cells with low and high VL, and correlation among HBV DNA titers and the fold-changes of PD-1 following anti-PD-L1 exposure. PD-L1; PD-ligand 1; CD, cluster of differentiation; CHB, chronic hepatits B; IL-2, interleukin 2; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; VL, viral levels.
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f3-mmr-14-02-1107: Anti-PD-L1 treatment and expression of CD28 family receptors. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients (n=22) were isolated and cultured in the presence of anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days. Cells were treated with anti-PD-L1 antibody or isotype antibody at a concentration of 5 µg/ml. (A) Representative flow cytometric dot plots of CD28 family receptors on CD4+ T cells with PD-1 blockade or isotype antibody treatment from a patient with CHB. (B) Expression of the receptors with PD-1 blockade or isotype antibody treatment. The fold-change of a single receptor was calculated by percentage following PD-1 blockade/before blockade. (C) Cumulative data showing fold-changes of PD-1 in CD4+ T cells with low and high VL, and correlation among HBV DNA titers and the fold-changes of PD-1 following anti-PD-L1 exposure. PD-L1; PD-ligand 1; CD, cluster of differentiation; CHB, chronic hepatits B; IL-2, interleukin 2; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; VL, viral levels.

Mentions: Besides assessing function, the effects of blocking PD-1 on the levels of co-stimulatory and co-inhibitory receptors were investigated. The expression of the CD28 family receptors and intracellular IFN-γ were measured simultaneously in T cells in HLA-A2+ patients with CHB following exposure to anti-PD-L1 or a control antibody. Increased expression of the receptors with PD-1 blockade or isotype antibody treatment are demonstrated by flow cytometric dot plots of peripheral CD4+ T cells from a patient with CHB (Fig. 3A). Following anti-PD-L1 exposure, the expression levels of CD28, ICOS, PD-1 and CTLA-4 were increased in the CD4+ T cells (Fig. 3B). No significant impact on the expression of the CD28 family receptors was observed on the CD8+ T cells following anti-PD-L1 exposure (Fig. 3B; P>0.05).


CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.

Tang ZS, Hao YH, Zhang EJ, Xu CL, Zhou Y, Zheng X, Yang DL - Mol Med Rep (2016)

Anti-PD-L1 treatment and expression of CD28 family receptors. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients (n=22) were isolated and cultured in the presence of anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days. Cells were treated with anti-PD-L1 antibody or isotype antibody at a concentration of 5 µg/ml. (A) Representative flow cytometric dot plots of CD28 family receptors on CD4+ T cells with PD-1 blockade or isotype antibody treatment from a patient with CHB. (B) Expression of the receptors with PD-1 blockade or isotype antibody treatment. The fold-change of a single receptor was calculated by percentage following PD-1 blockade/before blockade. (C) Cumulative data showing fold-changes of PD-1 in CD4+ T cells with low and high VL, and correlation among HBV DNA titers and the fold-changes of PD-1 following anti-PD-L1 exposure. PD-L1; PD-ligand 1; CD, cluster of differentiation; CHB, chronic hepatits B; IL-2, interleukin 2; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; VL, viral levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940091&req=5

f3-mmr-14-02-1107: Anti-PD-L1 treatment and expression of CD28 family receptors. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients (n=22) were isolated and cultured in the presence of anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days. Cells were treated with anti-PD-L1 antibody or isotype antibody at a concentration of 5 µg/ml. (A) Representative flow cytometric dot plots of CD28 family receptors on CD4+ T cells with PD-1 blockade or isotype antibody treatment from a patient with CHB. (B) Expression of the receptors with PD-1 blockade or isotype antibody treatment. The fold-change of a single receptor was calculated by percentage following PD-1 blockade/before blockade. (C) Cumulative data showing fold-changes of PD-1 in CD4+ T cells with low and high VL, and correlation among HBV DNA titers and the fold-changes of PD-1 following anti-PD-L1 exposure. PD-L1; PD-ligand 1; CD, cluster of differentiation; CHB, chronic hepatits B; IL-2, interleukin 2; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; VL, viral levels.
Mentions: Besides assessing function, the effects of blocking PD-1 on the levels of co-stimulatory and co-inhibitory receptors were investigated. The expression of the CD28 family receptors and intracellular IFN-γ were measured simultaneously in T cells in HLA-A2+ patients with CHB following exposure to anti-PD-L1 or a control antibody. Increased expression of the receptors with PD-1 blockade or isotype antibody treatment are demonstrated by flow cytometric dot plots of peripheral CD4+ T cells from a patient with CHB (Fig. 3A). Following anti-PD-L1 exposure, the expression levels of CD28, ICOS, PD-1 and CTLA-4 were increased in the CD4+ T cells (Fig. 3B). No significant impact on the expression of the CD28 family receptors was observed on the CD8+ T cells following anti-PD-L1 exposure (Fig. 3B; P>0.05).

Bottom Line: The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals.A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml.A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD‑1 blockade on the receptor expression profiles and the levels of interferon (IFN)‑γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T‑box 21 (T‑bet) and GATA binding protein 3 (GATA‑3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD‑1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T‑bet/GATA‑3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid monitoring of changes in T cell function during CHB treatment. Furthermore, PD‑1 blockade has a therapeutic potential that may be enhanced by modulating the expression of co-stimulatory and -inhibitory receptors of the CD28 family.

No MeSH data available.


Related in: MedlinePlus