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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.


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Expression of CD28 family receptors associated with the HBV DNA levels. Patients were classified as low (n=27) and high (n=25) VL, and CD4 or CD8 cells expressing CD28 family receptors were analyzed. (A) PD-1 and (B) BTLA on CD8 T cells were positively correlated with VL, (C) ICOS were inversely correlated, while (D) CD28 and (E) CTLA-4 demonstrated no correlation with HBV DNA levels. (F) Cumulative PD-1 expression data on CD8+ T cells in HBeAg+ (n=19) and HBeAg− groups (n=33). Data are presented as the mean ± standard error. CD, cluster of differentiation; HBV, hepatitis B virus; PD-1, programmed cell death protein 1; BTLA, B- and T-lymphocyte attenuator; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HBeAg, hepatitis E antigen; VL, viral levels.
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f2-mmr-14-02-1107: Expression of CD28 family receptors associated with the HBV DNA levels. Patients were classified as low (n=27) and high (n=25) VL, and CD4 or CD8 cells expressing CD28 family receptors were analyzed. (A) PD-1 and (B) BTLA on CD8 T cells were positively correlated with VL, (C) ICOS were inversely correlated, while (D) CD28 and (E) CTLA-4 demonstrated no correlation with HBV DNA levels. (F) Cumulative PD-1 expression data on CD8+ T cells in HBeAg+ (n=19) and HBeAg− groups (n=33). Data are presented as the mean ± standard error. CD, cluster of differentiation; HBV, hepatitis B virus; PD-1, programmed cell death protein 1; BTLA, B- and T-lymphocyte attenuator; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HBeAg, hepatitis E antigen; VL, viral levels.

Mentions: 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 viremia levels >106 IU/ml (P<0.0001; Fig. 2A). A significant positive correlation was observed among the serum HBV DNA titers and the expression levels of BTLA on CD8+T cells with the highest expression of BTLA corresponding to viremia levels >106 IU/ml (P<0.0001; Fig. 2B). However, a significant inverse correlation was indicated among the serum HBV DNA titers and expression levels of ICOS on CD8+ T cells with the lowest expression of ICOS corresponding to viremia levels >106 IU/ml (P<0.001; Fig. 2C). No significant difference was demonstrated compared with the healthy controls (P>0.05; Fig. 2C). No correlation was observed among the serum HBV DNA titers and expression levels of CD28 (Fig. 2D) or CTLA-4 (Fig. 2E) on CD8+ T cells. In addition, no correlations were observed among the virological parameters and the abnormal expression of the CD28 family receptors on CD4+ T cells in patients with CHB (data not shown). Furthermore, expression of PD-1 on CD8+ T cells was significantly higher in the HBeAg+ group compared with the HBeAg− group (P<0.0001; Fig. 2F).


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 associated with the HBV DNA levels. Patients were classified as low (n=27) and high (n=25) VL, and CD4 or CD8 cells expressing CD28 family receptors were analyzed. (A) PD-1 and (B) BTLA on CD8 T cells were positively correlated with VL, (C) ICOS were inversely correlated, while (D) CD28 and (E) CTLA-4 demonstrated no correlation with HBV DNA levels. (F) Cumulative PD-1 expression data on CD8+ T cells in HBeAg+ (n=19) and HBeAg− groups (n=33). Data are presented as the mean ± standard error. CD, cluster of differentiation; HBV, hepatitis B virus; PD-1, programmed cell death protein 1; BTLA, B- and T-lymphocyte attenuator; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HBeAg, hepatitis E antigen; VL, viral levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-14-02-1107: Expression of CD28 family receptors associated with the HBV DNA levels. Patients were classified as low (n=27) and high (n=25) VL, and CD4 or CD8 cells expressing CD28 family receptors were analyzed. (A) PD-1 and (B) BTLA on CD8 T cells were positively correlated with VL, (C) ICOS were inversely correlated, while (D) CD28 and (E) CTLA-4 demonstrated no correlation with HBV DNA levels. (F) Cumulative PD-1 expression data on CD8+ T cells in HBeAg+ (n=19) and HBeAg− groups (n=33). Data are presented as the mean ± standard error. CD, cluster of differentiation; HBV, hepatitis B virus; PD-1, programmed cell death protein 1; BTLA, B- and T-lymphocyte attenuator; ICOS, inducible T-cell co-stimulator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HBeAg, hepatitis E antigen; VL, viral levels.
Mentions: 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 viremia levels >106 IU/ml (P<0.0001; Fig. 2A). A significant positive correlation was observed among the serum HBV DNA titers and the expression levels of BTLA on CD8+T cells with the highest expression of BTLA corresponding to viremia levels >106 IU/ml (P<0.0001; Fig. 2B). However, a significant inverse correlation was indicated among the serum HBV DNA titers and expression levels of ICOS on CD8+ T cells with the lowest expression of ICOS corresponding to viremia levels >106 IU/ml (P<0.001; Fig. 2C). No significant difference was demonstrated compared with the healthy controls (P>0.05; Fig. 2C). No correlation was observed among the serum HBV DNA titers and expression levels of CD28 (Fig. 2D) or CTLA-4 (Fig. 2E) on CD8+ T cells. In addition, no correlations were observed among the virological parameters and the abnormal expression of the CD28 family receptors on CD4+ T cells in patients with CHB (data not shown). Furthermore, expression of PD-1 on CD8+ T cells was significantly higher in the HBeAg+ group compared with the HBeAg− group (P<0.0001; Fig. 2F).

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