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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

Expression of CD28 family receptors on CD4+ and CD8+ T cells of patients with CHB. Peripheral blood mononuclear cells were isolated from healthy donors (n=26) or patients with CHB (n=52), and stained with anti-CD4, CD8, CD28, CTLA-4, PD-1, ICOS, BTLA or isotype control antibodies. Dead cells were excluded by 7-AAD staining. (A) Representative flow cytometric scatter plots of CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB. (B and C) Expression of CD28, CTLA-4, PD-1, ICOS and BTLA receptors. CD, cluster of differentiation; CHB, chronic hepatitis B; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; BTLA, B- and T-lymphocyte attenuator; 7-AAD, 7-aminoactinomycin D.
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f1-mmr-14-02-1107: Expression of CD28 family receptors on CD4+ and CD8+ T cells of patients with CHB. Peripheral blood mononuclear cells were isolated from healthy donors (n=26) or patients with CHB (n=52), and stained with anti-CD4, CD8, CD28, CTLA-4, PD-1, ICOS, BTLA or isotype control antibodies. Dead cells were excluded by 7-AAD staining. (A) Representative flow cytometric scatter plots of CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB. (B and C) Expression of CD28, CTLA-4, PD-1, ICOS and BTLA receptors. CD, cluster of differentiation; CHB, chronic hepatitis B; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; BTLA, B- and T-lymphocyte attenuator; 7-AAD, 7-aminoactinomycin D.

Mentions: To compare the in vitro expression frequency of the CD28 family, 5 receptors on total peripheral CD4+ and CD8+ T cells from patients with CHB (n=52) and healthy controls (n=26) were investigated. Representative flow cytometric scatter plots of the CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB are demonstrated in Fig. 1A. Levels of PD-1 and CTLA-4 on CD4 T cells (Fig. 1B) and ICOS, PD-1, and BTLA on CD8 T cells (Fig. 1C) were increased in cells from patients with CHB compared with those from the healthy controls.


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)

Expression of CD28 family receptors on CD4+ and CD8+ T cells of patients with CHB. Peripheral blood mononuclear cells were isolated from healthy donors (n=26) or patients with CHB (n=52), and stained with anti-CD4, CD8, CD28, CTLA-4, PD-1, ICOS, BTLA or isotype control antibodies. Dead cells were excluded by 7-AAD staining. (A) Representative flow cytometric scatter plots of CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB. (B and C) Expression of CD28, CTLA-4, PD-1, ICOS and BTLA receptors. CD, cluster of differentiation; CHB, chronic hepatitis B; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; BTLA, B- and T-lymphocyte attenuator; 7-AAD, 7-aminoactinomycin D.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-mmr-14-02-1107: Expression of CD28 family receptors on CD4+ and CD8+ T cells of patients with CHB. Peripheral blood mononuclear cells were isolated from healthy donors (n=26) or patients with CHB (n=52), and stained with anti-CD4, CD8, CD28, CTLA-4, PD-1, ICOS, BTLA or isotype control antibodies. Dead cells were excluded by 7-AAD staining. (A) Representative flow cytometric scatter plots of CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB. (B and C) Expression of CD28, CTLA-4, PD-1, ICOS and BTLA receptors. CD, cluster of differentiation; CHB, chronic hepatitis B; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; ICOS, inducible T-cell co-stimulator; BTLA, B- and T-lymphocyte attenuator; 7-AAD, 7-aminoactinomycin D.
Mentions: To compare the in vitro expression frequency of the CD28 family, 5 receptors on total peripheral CD4+ and CD8+ T cells from patients with CHB (n=52) and healthy controls (n=26) were investigated. Representative flow cytometric scatter plots of the CD28 family receptors on peripheral CD4+ and CD8+ T cells from a patient with CHB are demonstrated in Fig. 1A. Levels of PD-1 and CTLA-4 on CD4 T cells (Fig. 1B) and ICOS, PD-1, and BTLA on CD8 T cells (Fig. 1C) were increased in cells from patients with CHB compared with those from the healthy controls.

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