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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

IFN-γ expression of CD4 T cells following PD-1 blockade. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were isolated and cultured with anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days in present of anti-PD-L1 or isotype control. Cells were harvested, restimulated and stained by intracellular IFN-γ staining. (A) The representative flow cytometric dot plots of IFN-γ levels in CD4+ and CD8+ T cells. (B) Comparing percentage of IFN-γ producing in CD4 or CD8 T cells treated with anti-PD-L1 or isotype antibody. (C) The ability of IFN-γ production was positively correlated with ICOS while inversely correlated with PD-1 expression on CD4 T cells. IFN-, interferon-; CHB, chronic hepatitis B; IL-2, interleukin-2; PD-L1, PD-Ligand 1.
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f4-mmr-14-02-1107: IFN-γ expression of CD4 T cells following PD-1 blockade. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were isolated and cultured with anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days in present of anti-PD-L1 or isotype control. Cells were harvested, restimulated and stained by intracellular IFN-γ staining. (A) The representative flow cytometric dot plots of IFN-γ levels in CD4+ and CD8+ T cells. (B) Comparing percentage of IFN-γ producing in CD4 or CD8 T cells treated with anti-PD-L1 or isotype antibody. (C) The ability of IFN-γ production was positively correlated with ICOS while inversely correlated with PD-1 expression on CD4 T cells. IFN-, interferon-; CHB, chronic hepatitis B; IL-2, interleukin-2; PD-L1, PD-Ligand 1.

Mentions: The representative flow cytometric dot plots of intracellular IFN-γ expression in CD4+ and CD8+ T cells with PD-1 blockade or isotype antibody treatment are demonstrated in Fig. 4. Following anti-PD-L1 treatment, the levels of IFN-γ were increased in CD4+ T cells (Fig. 4B) and IFN-γ fold changes in CD4+ T cells had a positive correlation with ICOS fold-change (P=0.0062; Fig. 4C). However, there was an inverse correlation with PD-1 fold-change (P=0.004; Fig. 4C). In the current study, no significant impact was demonstrated on the expression of IFN-γ in the CD8+ T cells following anti-PD-L1 treatment (Fig. 4B; 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)

IFN-γ expression of CD4 T cells following PD-1 blockade. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were isolated and cultured with anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days in present of anti-PD-L1 or isotype control. Cells were harvested, restimulated and stained by intracellular IFN-γ staining. (A) The representative flow cytometric dot plots of IFN-γ levels in CD4+ and CD8+ T cells. (B) Comparing percentage of IFN-γ producing in CD4 or CD8 T cells treated with anti-PD-L1 or isotype antibody. (C) The ability of IFN-γ production was positively correlated with ICOS while inversely correlated with PD-1 expression on CD4 T cells. IFN-, interferon-; CHB, chronic hepatitis B; IL-2, interleukin-2; PD-L1, PD-Ligand 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-14-02-1107: IFN-γ expression of CD4 T cells following PD-1 blockade. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were isolated and cultured with anti-CD28, IL-2 and HBcAg18-27 peptide for 10 days in present of anti-PD-L1 or isotype control. Cells were harvested, restimulated and stained by intracellular IFN-γ staining. (A) The representative flow cytometric dot plots of IFN-γ levels in CD4+ and CD8+ T cells. (B) Comparing percentage of IFN-γ producing in CD4 or CD8 T cells treated with anti-PD-L1 or isotype antibody. (C) The ability of IFN-γ production was positively correlated with ICOS while inversely correlated with PD-1 expression on CD4 T cells. IFN-, interferon-; CHB, chronic hepatitis B; IL-2, interleukin-2; PD-L1, PD-Ligand 1.
Mentions: The representative flow cytometric dot plots of intracellular IFN-γ expression in CD4+ and CD8+ T cells with PD-1 blockade or isotype antibody treatment are demonstrated in Fig. 4. Following anti-PD-L1 treatment, the levels of IFN-γ were increased in CD4+ T cells (Fig. 4B) and IFN-γ fold changes in CD4+ T cells had a positive correlation with ICOS fold-change (P=0.0062; Fig. 4C). However, there was an inverse correlation with PD-1 fold-change (P=0.004; Fig. 4C). In the current study, no significant impact was demonstrated on the expression of IFN-γ in the CD8+ T cells following anti-PD-L1 treatment (Fig. 4B; 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